Guide to using MR-TRYX
Yoonsu Cho
guide.RmdThe following analyses should run within a couple of minutes, depending on internet speed and the traffic that the IEU GWAS database servers are experiencing.
Begin by choosing an exposure-outcome hypothesis to explore. e.g. LDL cholesterol on coronary heart disease. These data can be extracted from the IEU GWAS database using the TwoSampleMR package:
Data setup
If necessary install TwoSampleMR:
devtools::install_github("mrcieu/TwoSampleMR@ieugwasr")
Create a dataset for SBP and CHD
library(TwoSampleMR) a <- extract_instruments("ukb-b-20175") #> API: public: http://gwas-api.mrcieu.ac.uk/ #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 b <- extract_outcome_data(a$SNP, "ieu-a-7", access_token=NULL) #> Extracting data for 244 SNP(s) from 1 GWAS(s) #> Finding proxies for 4 SNPs in outcome ieu-a-7 #> Extracting data for 4 SNP(s) from 1 GWAS(s) dat <- harmonise_data(a,b) #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Coronary heart disease || id:ieu-a-7 (ieu-a-7) #> Removing the following SNPs for incompatible alleles: #> rs17811915 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs2246832, rs28470858, rs28667801
Running Tryx
We can now perform the analysis:
This will do the following:
- Initialise the Tryx class with the
datobject we already created - Find outlier SNPs in the exposure-outcome analysis
- Find traits in the IEU GWAS database that those outliers associate with. These traits are known as ‘candidate traits’
- Extract instruments for those ‘candidate traits’
- Perform MR of each of those ‘candidate traits’ against the exposure and the outcome
library(tryx) x <- Tryx$new(dat) x$mrtryx() #> Using RadialMR package to detect outliers #> #> Radial IVW #> #> Estimate Std.Error t value Pr(>|t|) #> Effect (Mod.2nd) 0.5991043 0.07718481 7.761945 8.363657e-15 #> Iterative 0.5991043 0.07718481 7.761945 8.363657e-15 #> Exact (FE) 0.6420699 0.04024276 15.954916 2.633294e-57 #> Exact (RE) 0.6101965 0.08857214 6.889260 5.227019e-11 #> #> #> Residual standard error: 1.92 on 232 degrees of freedom #> #> F-statistic: 60.25 on 1 and 232 DF, p-value: 2.66e-13 #> Q-Statistic for heterogeneity: 855.6769 on 232 DF , p-value: 2.874833e-72 #> #> Outliers detected #> Number of iterations = 2 #> Warning in if (radial$outliers[1] == "No significant outliers") {: the condition #> has length > 1 and only the first element will be used #> Identified 11 outliers #> Using default list of 6467 traits #> Extracting data for 11 SNP(s) from 6467 GWAS(s) #> Found 139 candidate traits associated with outliers at p < 5e-08 #> Finding instruments for candidate traits #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '3mm strong meridian (left) || id:ukb-b-14664. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '3mm strong meridian (right) || id:ukb-b-6852. Just keeping the first instance: #> rs2242398 #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '3mm weak meridian (left) || id:ukb-b-11113. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '3mm weak meridian (right) || id:ukb-b-13506. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '6mm strong meridian (right) || id:ukb-b-11452. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '6mm weak meridian (left) || id:ukb-b-13538. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype '6mm weak meridian (right) || id:ukb-b-13416. Just keeping the first instance: #> rs8047844 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Alcohol intake frequency. || id:ukb-b-5779. Just keeping the first instance: #> rs9958320 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Ankle spacing width || id:ukb-b-4080. Just keeping the first instance: #> rs3732360 #> rs1294438 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Arm fat percentage (left) || id:ukb-b-20188. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Arm fat-free mass (right) || id:ukb-b-19520. Just keeping the first instance: #> rs3740591 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Basal metabolic rate || id:ukb-b-16446. Just keeping the first instance: #> rs3129962 #> rs3740591 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Birth weight || id:ukb-b-13378. Just keeping the first instance: #> rs2140240 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Blood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor: Asthma || id:ukb-b-20296. Just keeping the first instance: #> rs35320232 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Blood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor: Hayfever, allergic rhinitis or eczema || id:ukb-b-17241. Just keeping the first instance: #> rs35320232 #> rs2075973 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Blood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor: None of the above || id:ukb-b-18200. Just keeping the first instance: #> rs35320232 #> rs2097431 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Body fat percentage || id:ukb-b-8909. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Diastolic blood pressure, automated reading || id:ukb-b-7992. Just keeping the first instance: #> rs28752924 #> rs17304212 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Duration to first press of snap-button in each round || id:ukb-b-19373. Just keeping the first instance: #> rs9304167 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Hip circumference || id:ukb-b-15590. Just keeping the first instance: #> rs1294438 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Impedance of arm (right) || id:ukb-b-7859. Just keeping the first instance: #> rs111650620 #> rs1382568 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Impedance of leg (left) || id:ukb-b-14068. Just keeping the first instance: #> rs776912 #> rs2952894 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Impedance of leg (right) || id:ukb-b-7376. Just keeping the first instance: #> rs776912 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat percentage (left) || id:ukb-b-18377. Just keeping the first instance: #> rs1428 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat percentage (right) || id:ukb-b-20531. Just keeping the first instance: #> rs7027096 #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat-free mass (left) || id:ukb-b-16099. Just keeping the first instance: #> rs3129962 #> rs77760034 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat-free mass (right) || id:ukb-b-12828. Just keeping the first instance: #> rs77760034 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg predicted mass (left) || id:ukb-b-17271. Just keeping the first instance: #> rs3129962 #> rs77760034 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg predicted mass (right) || id:ukb-b-14310. Just keeping the first instance: #> rs77760034 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014. Just keeping the first instance: #> rs2209042 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: None of the above || id:ukb-b-20379. Just keeping the first instance: #> rs13204736 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Medication for pain relief, constipation, heartburn: Paracetamol || id:ukb-b-17595. Just keeping the first instance: #> rs34555420 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Non-cancer illness code, self-reported: asthma || id:ukb-b-18113. Just keeping the first instance: #> rs17142799 #> rs35320232 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057. Just keeping the first instance: #> rs4783581 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Number of self-reported non-cancer illnesses || id:ukb-b-4063. Just keeping the first instance: #> rs13204736 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Pain type(s) experienced in last month: Headache || id:ukb-b-12181. Just keeping the first instance: #> rs34555420 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Peak expiratory flow (PEF) || id:ukb-b-12019. Just keeping the first instance: #> rs2666547 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Sitting height || id:ukb-b-16881. Just keeping the first instance: #> rs4651157 #> rs872937 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Standing height || id:ukb-b-10787. Just keeping the first instance: #> rs11252860 #> rs34773647 #> rs664317 #> rs7978217 #> rs11051456 #> rs1019075 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Treatment/medication code: amlodipine || id:ukb-b-9207. Just keeping the first instance: #> rs2077111 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat mass || id:ukb-b-20044. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat percentage || id:ukb-b-16407. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat-free mass || id:ukb-b-17409. Just keeping the first instance: #> rs3735352 #> rs3740591 #> rs1040457 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk predicted mass || id:ukb-b-9685. Just keeping the first instance: #> rs77760034 #> rs3735352 #> rs7978217 #> rs1040457 #> rs3740591 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177. Just keeping the first instance: #> rs4783581 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352. Just keeping the first instance: #> rs4783581 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Whole body fat-free mass || id:ukb-b-13354. Just keeping the first instance: #> rs434072 #> rs3740591 #> rs1040457 #> rs77760034 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Whole body water mass || id:ukb-b-14540. Just keeping the first instance: #> rs1040457 #> rs3740591 #> rs77760034 #> Warning in format_data(d, type = "exposure", snps = NULL, phenotype_col = #> "phenotype", : eaf column is not numeric. Coercing... #> Removing outlier SNPs from candidate trait instrument lists #> 139 traits with at least one instrument #> Looking up candidate trait instruments for Coronary heart disease || id:ieu-a-7 #> Extracting data for 10546 SNP(s) from 1 GWAS(s) #> 1 of 1 outcomes #> [>] 1 of 2 chunks #> [>] 2 of 2 chunks #> 10339 instruments extracted for Coronary heart disease || id:ieu-a-7 #> Looking up candidate trait instruments for Systolic blood pressure, automated reading || id:ukb-b-20175 #> Extracting data for 10546 SNP(s) from 1 GWAS(s) #> 1 of 1 outcomes #> [>] 1 of 2 chunks #> [>] 2 of 2 chunks #> instruments extracted for Systolic blood pressure, automated reading || id:ukb-b-20175 #> Looking up exposure instruments for 139 candidate traits #> Extracting data for 233 SNP(s) from 139 GWAS(s) #> 30833 instruments extracted #> Removing outlier SNPs from candidate trait outcome lists #> Removed 212 outlier SNPs #> Performing MR of 139 candidate traits against Coronary heart disease || id:ieu-a-7 #> Performing MR of 139 candidate traits against Systolic blood pressure, automated reading || id:ukb-b-20175 #> Performing MR of Systolic blood pressure, automated reading || id:ukb-b-20175 against 139 candidate traits
Step-by-step analysis
The analysis performed by mrtryx() can be broken down into multiple steps, running the following commands:
# Find outlier SNPs in the exposure-outcome analysis x$get_outliers() # Find traits in the MR-Base database that those outliers associate with. These traits are known as 'candidate traits' x$set_candidate_traits() x$scan()
Note that you can browse available traits here: https://gwas.mrcieu.ac.uk/ and get a complete list using:
traits <- TwoSampleMR::available_outcomes()
# Extract instruments for those 'candidate traits' x$extractions() #which includes the following functions: x$candidate_instruments() x$outcome_instruments() x$exposure_instruments() x$exposure_candidate_instruments() # Make datasets for MR analysis x$harmonise() #which includes the following functions: x$candidate_outcome_dat() x$candidate_exposure_dat() x$exposure_candidate_dat() # Perform MR of each of those 'candidate traits' against the exposure and the outcomes x$mr()
See the ?Tryx for options on the parameters for this analysis. e.g. You can specify your own set of outliers, for example SNPs that have extreme p-values in the outcome GWAS
a <- as.character(subset(dat, pval.outcome < 5e-8)$SNP) x <- Tryx$new(dat) x$mrtryx(outliers=a)
The next steps are to determine which of the candidate traits are of interest (e.g. using p-value thresholds), visualise the results, and adjust the exposure-outcome estimates based on knowledge of the ‘candidate trait’ associations.
Significant candidate traits
One can determine which of the putative associations might be ‘interesting’ in different ways. We have provided a simple convenience function to apply different multiple testing corrections. e.g.
x$tryx.sig() #> Adjusting p-value #> * * * * #> Number of candidate - outcome associations: 78 #> * * * * #> Large vessel disease || id:ieu-a-1110 #> HDL cholesterol || id:ieu-a-299 #> LDL cholesterol || id:ieu-a-300 #> Total cholesterol || id:ieu-a-301 #> Myocardial infarction || id:ieu-a-798 #> Interleukin-2 receptor subunit beta || id:prot-a-1519 #> Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 #> Illnesses of mother: None of the above (group 1) || id:ukb-b-10454 #> Age high blood pressure diagnosed || id:ukb-b-1061 #> Standing height || id:ukb-b-10787 #> Diagnoses - secondary ICD10: Z95.1 Presence of aortocoronary bypass graft || id:ukb-b-11064 #> Father's age at death || id:ukb-b-11303 #> Vascular/heart problems diagnosed by doctor: Heart attack || id:ukb-b-11590 #> Treatment/medication code: atenolol || id:ukb-b-11632 #> Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 #> Weight || id:ukb-b-11842 #> Treatment/medication code: ramipril || id:ukb-b-11895 #> Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> Operation code: coronary artery bypass grafts (cabg) || id:ukb-b-12465 #> Illnesses of mother: Heart disease || id:ukb-b-12477 #> Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> Treatment speciality of consultant (recoded): General medicine || id:ukb-b-12646 #> Arm fat percentage (right) || id:ukb-b-12854 #> Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> Birth weight || id:ukb-b-13378 #> 3mm weak meridian (right) || id:ukb-b-13506 #> Long-standing illness, disability or infirmity || id:ukb-b-13764 #> Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> Illnesses of siblings: Heart disease || id:ukb-b-14371 #> Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> Illnesses of father: None of the above (group 1) || id:ukb-b-15169 #> Operative procedures - main OPCS: K45.3 Anastomosis of mammary artery to left anterior descending coronary artery || id:ukb-b-15491 #> Hip circumference || id:ukb-b-15590 #> Diagnoses - secondary ICD10: I20.9 Angina pectoris, unspecified || id:ukb-b-15686 #> Diagnoses - secondary ICD10: Z95.5 Presence of coronary angioplasty implant and graft || id:ukb-b-15748 #> Non-cancer illness code, self-reported: heart attack/myocardial infarction || id:ukb-b-15829 #> Main speciality of consultant (recoded): Cardiology || id:ukb-b-16376 #> Trunk fat percentage || id:ukb-b-16407 #> Diagnoses - secondary ICD10: I25.8 Other forms of chronic ischaemic heart disease || id:ukb-b-16606 #> Diagnoses - main ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-1668 #> Treatment/medication code: ibuprofen || id:ukb-b-16866 #> Sitting height || id:ukb-b-16881 #> Illnesses of siblings: None of the above (group 1) || id:ukb-b-17360 #> Trunk fat-free mass || id:ukb-b-17409 #> Operative procedures - secondary OPCS: Y02.2 Insertion of prosthesis into organ NOC || id:ukb-b-1744 #> Treatment/medication code: levothyroxine sodium || id:ukb-b-17918 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> Operative procedures - main OPCS: K49.1 Percutaneous transluminal balloon angioplasty of one coronary artery || id:ukb-b-18018 #> Illnesses of mother: High blood pressure || id:ukb-b-18167 #> Leg fat percentage (left) || id:ukb-b-18377 #> Illnesses of father: Heart disease || id:ukb-b-18408 #> Treatment/medication code: bendroflumethiazide || id:ukb-b-18799 #> Impedance of arm (left) || id:ukb-b-19379 #> Non-cancer illness code, self-reported: hypothyroidism/myxoedema || id:ukb-b-19732 #> Impedance of whole body || id:ukb-b-19921 #> Trunk fat mass || id:ukb-b-20044 #> Arm fat percentage (left) || id:ukb-b-20188 #> Taking other prescription medications || id:ukb-b-20292 #> Treatment speciality of consultant (recoded): Cardiology || id:ukb-b-20300 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: None of the above || id:ukb-b-20379 #> Leg fat percentage (right) || id:ukb-b-20531 #> Birth weight of first child || id:ukb-b-3357 #> Number of treatments/medications taken || id:ukb-b-3656 #> Number of self-reported non-cancer illnesses || id:ukb-b-4063 #> Diagnoses - secondary ICD10: E03.9 Hypothyroidism, unspecified || id:ukb-b-4226 #> Medication for pain relief, constipation, heartburn: Aspirin || id:ukb-b-7137 #> Diagnoses - secondary ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-7436 #> Impedance of arm (right) || id:ukb-b-7859 #> Operation code: coronary angioplasty (ptca) +/- stent || id:ukb-b-7869 #> Diastolic blood pressure, automated reading || id:ukb-b-7992 #> Vascular/heart problems diagnosed by doctor: Angina || id:ukb-b-8468 #> Non-cancer illness code, self-reported: angina || id:ukb-b-8650 #> Illnesses of siblings: High blood pressure || id:ukb-b-8746 #> Treatment/medication code: aspirin || id:ukb-b-8755 #> Body fat percentage || id:ukb-b-8909 #> Treatment/medication code: amlodipine || id:ukb-b-9207 #> #> * * * * #> Number of candidate - exposure associations: 68 #> * * * * #> Large vessel disease || id:ieu-a-1110 #> Interleukin-2 receptor subunit beta || id:prot-a-1519 #> Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 #> Illnesses of mother: None of the above (group 1) || id:ukb-b-10454 #> Age high blood pressure diagnosed || id:ukb-b-1061 #> Standing height || id:ukb-b-10787 #> Treatment/medication code: atenolol || id:ukb-b-11632 #> Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 #> Treatment/medication code: ramipril || id:ukb-b-11895 #> Pulse wave Arterial Stiffness index || id:ukb-b-11971 #> Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> Peak expiratory flow (PEF) || id:ukb-b-12019 #> Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> Leg fat-free mass (right) || id:ukb-b-12828 #> Arm fat percentage (right) || id:ukb-b-12854 #> Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> Whole body fat-free mass || id:ukb-b-13354 #> Birth weight || id:ukb-b-13378 #> 6mm weak meridian (right) || id:ukb-b-13416 #> 3mm weak meridian (right) || id:ukb-b-13506 #> Long-standing illness, disability or infirmity || id:ukb-b-13764 #> Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> Leg predicted mass (right) || id:ukb-b-14310 #> Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> Whole body water mass || id:ukb-b-14540 #> 3mm strong meridian (left) || id:ukb-b-14664 #> Leg fat-free mass (left) || id:ukb-b-16099 #> Trunk fat percentage || id:ukb-b-16407 #> Basal metabolic rate || id:ukb-b-16446 #> Arm predicted mass (right) || id:ukb-b-16698 #> Treatment/medication code: ibuprofen || id:ukb-b-16866 #> Sitting height || id:ukb-b-16881 #> Leg predicted mass (left) || id:ukb-b-17271 #> Illnesses of siblings: None of the above (group 1) || id:ukb-b-17360 #> Trunk fat-free mass || id:ukb-b-17409 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> Non-cancer illness code, self-reported: asthma || id:ukb-b-18113 #> Illnesses of mother: High blood pressure || id:ukb-b-18167 #> Leg fat percentage (left) || id:ukb-b-18377 #> Treatment/medication code: bendroflumethiazide || id:ukb-b-18799 #> Impedance of arm (left) || id:ukb-b-19379 #> Illnesses of father: High blood pressure || id:ukb-b-19456 #> Impedance of whole body || id:ukb-b-19921 #> Arm fat-free mass (left) || id:ukb-b-19925 #> Trunk fat mass || id:ukb-b-20044 #> Arm fat percentage (left) || id:ukb-b-20188 #> Ever smoked || id:ukb-b-20261 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: None of the above || id:ukb-b-20379 #> Leg fat percentage (right) || id:ukb-b-20531 #> Birth weight of first child || id:ukb-b-3357 #> Number of treatments/medications taken || id:ukb-b-3656 #> Operation code: hysterectomy || id:ukb-b-3700 #> Number of self-reported non-cancer illnesses || id:ukb-b-4063 #> Lifetime number of sexual partners || id:ukb-b-4256 #> 6mm strong meridian (left) || id:ukb-b-645 #> Impedance of arm (right) || id:ukb-b-7859 #> Diastolic blood pressure, automated reading || id:ukb-b-7992 #> Vascular/heart problems diagnosed by doctor: Angina || id:ukb-b-8468 #> Non-cancer illness code, self-reported: angina || id:ukb-b-8650 #> Illnesses of siblings: High blood pressure || id:ukb-b-8746 #> Treatment/medication code: aspirin || id:ukb-b-8755 #> Pulse wave peak to peak time || id:ukb-b-8778 #> Body fat percentage || id:ukb-b-8909 #> Arm predicted mass (left) || id:ukb-b-9093 #> Treatment/medication code: amlodipine || id:ukb-b-9207 #> Trunk predicted mass || id:ukb-b-9685 #> #> * * * * #> Number of exposure - candidate associations: 89 #> * * * * #> Large vessel disease || id:ieu-a-1110 #> Interleukin-2 receptor subunit beta || id:prot-a-1519 #> Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 #> Illnesses of mother: None of the above (group 1) || id:ukb-b-10454 #> Age high blood pressure diagnosed || id:ukb-b-1061 #> Standing height || id:ukb-b-10787 #> Treatment/medication code: atenolol || id:ukb-b-11632 #> Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 #> Treatment/medication code: ramipril || id:ukb-b-11895 #> Pulse wave Arterial Stiffness index || id:ukb-b-11971 #> Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> Peak expiratory flow (PEF) || id:ukb-b-12019 #> Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> Leg fat-free mass (right) || id:ukb-b-12828 #> Arm fat percentage (right) || id:ukb-b-12854 #> Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> Whole body fat-free mass || id:ukb-b-13354 #> Birth weight || id:ukb-b-13378 #> 6mm weak meridian (right) || id:ukb-b-13416 #> 3mm weak meridian (right) || id:ukb-b-13506 #> Long-standing illness, disability or infirmity || id:ukb-b-13764 #> Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> Leg predicted mass (right) || id:ukb-b-14310 #> Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> Whole body water mass || id:ukb-b-14540 #> 3mm strong meridian (left) || id:ukb-b-14664 #> Leg fat-free mass (left) || id:ukb-b-16099 #> Trunk fat percentage || id:ukb-b-16407 #> Basal metabolic rate || id:ukb-b-16446 #> Arm predicted mass (right) || id:ukb-b-16698 #> Treatment/medication code: ibuprofen || id:ukb-b-16866 #> Sitting height || id:ukb-b-16881 #> Leg predicted mass (left) || id:ukb-b-17271 #> Illnesses of siblings: None of the above (group 1) || id:ukb-b-17360 #> Trunk fat-free mass || id:ukb-b-17409 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> Non-cancer illness code, self-reported: asthma || id:ukb-b-18113 #> Illnesses of mother: High blood pressure || id:ukb-b-18167 #> Leg fat percentage (left) || id:ukb-b-18377 #> Treatment/medication code: bendroflumethiazide || id:ukb-b-18799 #> Impedance of arm (left) || id:ukb-b-19379 #> Illnesses of father: High blood pressure || id:ukb-b-19456 #> Impedance of whole body || id:ukb-b-19921 #> Arm fat-free mass (left) || id:ukb-b-19925 #> Trunk fat mass || id:ukb-b-20044 #> Arm fat percentage (left) || id:ukb-b-20188 #> Ever smoked || id:ukb-b-20261 #> Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: None of the above || id:ukb-b-20379 #> Leg fat percentage (right) || id:ukb-b-20531 #> Birth weight of first child || id:ukb-b-3357 #> Number of treatments/medications taken || id:ukb-b-3656 #> Operation code: hysterectomy || id:ukb-b-3700 #> Number of self-reported non-cancer illnesses || id:ukb-b-4063 #> Lifetime number of sexual partners || id:ukb-b-4256 #> 6mm strong meridian (left) || id:ukb-b-645 #> Impedance of arm (right) || id:ukb-b-7859 #> Diastolic blood pressure, automated reading || id:ukb-b-7992 #> Vascular/heart problems diagnosed by doctor: Angina || id:ukb-b-8468 #> Non-cancer illness code, self-reported: angina || id:ukb-b-8650 #> Illnesses of siblings: High blood pressure || id:ukb-b-8746 #> Treatment/medication code: aspirin || id:ukb-b-8755 #> Pulse wave peak to peak time || id:ukb-b-8778 #> Body fat percentage || id:ukb-b-8909 #> Arm predicted mass (left) || id:ukb-b-9093 #> Treatment/medication code: amlodipine || id:ukb-b-9207 #> Trunk predicted mass || id:ukb-b-9685
Will by default use FDR of 5%. See ?Tryx for more options.
Adjustment
Finally, to adjust the SNP effects on the exposure and outcome traits given their influences on the candidate traits, we can run:
x$analyse() #> p->y: rs9349379 - Diagnoses - secondary ICD10: I20.9 Angina pectoris, unspecified || id:ukb-b-15686 #> x<-p->y: rs10774625 - Birth weight || id:ukb-b-13378 #> p->y: rs6430078 - Illnesses of father: Heart disease || id:ukb-b-18408 #> x<-p->y: rs10774625 - Long-standing illness, disability or infirmity || id:ukb-b-13764 #> x<-p->y: rs10774625 - Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> x<-p->y: rs2681492 - Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> x<-p->y: rs10774625 - Treatment/medication code: aspirin || id:ukb-b-8755 #> x<-p->y: rs10774625 - Treatment/medication code: atenolol || id:ukb-b-11632 #> x<-p->y: rs10774625 - Illnesses of siblings: High blood pressure || id:ukb-b-8746 #> p->y: rs9349379 - Illnesses of siblings: Heart disease || id:ukb-b-14371 #> x<-p->y: rs2681492 - Treatment/medication code: bendroflumethiazide || id:ukb-b-18799 #> x<-p->y: rs57866767 - Treatment/medication code: amlodipine || id:ukb-b-9207 #> p->y: rs9349379 - Operation code: coronary angioplasty (ptca) +/- stent || id:ukb-b-7869 #> p->y: rs10774625 - Treatment speciality of consultant (recoded): Cardiology || id:ukb-b-20300 #> x<-p->y: rs57866767 - Impedance of arm (left) || id:ukb-b-19379 #> x<-p->y: rs35114617 - Sitting height || id:ukb-b-16881 #> x<-p->y: rs8027450 - Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> p->y: rs9349379 - Illnesses of mother: Heart disease || id:ukb-b-12477 #> p->y: rs10774625 - Vascular/heart problems diagnosed by doctor: Heart attack || id:ukb-b-11590 #> x<-p->y: rs2681492 - Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> p->y: rs9349379 - Diagnoses - secondary ICD10: Z95.5 Presence of coronary angioplasty implant and graft || id:ukb-b-15748 #> x<-p->y: rs57866767 - 3mm weak meridian (right) || id:ukb-b-13506 #> p->y: rs10774625 - Hip circumference || id:ukb-b-15590 #> p->y: rs10774625 - Illnesses of father: None of the above (group 1) || id:ukb-b-15169 #> p->y: rs8027450 - Illnesses of father: None of the above (group 1) || id:ukb-b-15169 #> x<-p->y: rs57866767 - Impedance of whole body || id:ukb-b-19921 #> x<-p->y: rs57866767 - Arm fat percentage (left) || id:ukb-b-20188 #> x<-p->y: rs57866767 - Birth weight || id:ukb-b-13378 #> p->y: rs9349379 - Diagnoses - secondary ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-7436 #> x<-p->y: rs10774625 - Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: None of the above || id:ukb-b-20379 #> p->y: rs10774625 - Diagnoses - secondary ICD10: E03.9 Hypothyroidism, unspecified || id:ukb-b-4226 #> x<-p->y: rs10774625 - Standing height || id:ukb-b-10787 #> p->y: rs9349379 - Operative procedures - secondary OPCS: Y02.2 Insertion of prosthesis into organ NOC || id:ukb-b-1744 #> x<-p->y: rs57866767 - Leg fat percentage (left) || id:ukb-b-18377 #> x<-p->y: rs57866767 - Body fat percentage || id:ukb-b-8909 #> x<-p->y: rs10774625 - Age high blood pressure diagnosed || id:ukb-b-1061 #> x<-p->y: rs8027450 - Illnesses of mother: High blood pressure || id:ukb-b-18167 #> p->y: rs10774625 - Medication for pain relief, constipation, heartburn: Aspirin || id:ukb-b-7137 #> p->y: rs9349379 - Non-cancer illness code, self-reported: heart attack/myocardial infarction || id:ukb-b-15829 #> p->y: rs9349379 - Diagnoses - secondary ICD10: I25.8 Other forms of chronic ischaemic heart disease || id:ukb-b-16606 #> x<-p->y: rs10774625 - Illnesses of siblings: None of the above (group 1) || id:ukb-b-17360 #> x<-p->y: rs57866767 - Leg fat percentage (right) || id:ukb-b-20531 #> x<-p->y: rs57866767 - Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> x<-p->y: rs10774625 - Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> x<-p->y: rs2681492 - Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> x<-p->y: rs57866767 - Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> p->y: rs10774625 - Diagnoses - secondary ICD10: Z95.5 Presence of coronary angioplasty implant and graft || id:ukb-b-15748 #> p->y: rs10774625 - Weight || id:ukb-b-11842 #> x<-p->y: rs8027450 - Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> x<-p->y: rs57866767 - Diastolic blood pressure, automated reading || id:ukb-b-7992 #> x<-p->y: rs2681492 - Diastolic blood pressure, automated reading || id:ukb-b-7992 #> p->y: rs10774625 - Diagnoses - secondary ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-7436 #> p->y: rs9349379 - Diagnoses - secondary ICD10: Z95.1 Presence of aortocoronary bypass graft || id:ukb-b-11064 #> x<-p->y: rs35114617 - Standing height || id:ukb-b-10787 #> p->y: rs10774625 - Non-cancer illness code, self-reported: hypothyroidism/myxoedema || id:ukb-b-19732 #> p->y: rs10774625 - Treatment/medication code: levothyroxine sodium || id:ukb-b-17918 #> x<-p->y: rs10774625 - Treatment/medication code: ramipril || id:ukb-b-11895 #> p->y: rs8027450 - Illnesses of father: Heart disease || id:ukb-b-18408 #> x<-p->y: rs8027450 - Illnesses of siblings: High blood pressure || id:ukb-b-8746 #> x<-p->y: rs57866767 - Arm fat percentage (right) || id:ukb-b-12854 #> x<-p->y: rs10774625 - Trunk fat-free mass || id:ukb-b-17409 #> p->y: rs9349379 - Operative procedures - main OPCS: K45.3 Anastomosis of mammary artery to left anterior descending coronary artery || id:ukb-b-15491 #> x<-p->y: rs8027450 - Birth weight of first child || id:ukb-b-3357 #> p->y: rs9349379 - Main speciality of consultant (recoded): Cardiology || id:ukb-b-16376 #> x<-p->y: rs8027450 - Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> x<-p->y: rs2681492 - Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> x<-p->y: rs57866767 - Impedance of arm (right) || id:ukb-b-7859 #> x<-p->y: rs10774625 - 3mm weak meridian (right) || id:ukb-b-13506 #> x<-p->y: rs57866767 - Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> x<-p->y: rs10774625 - Impedance of whole body || id:ukb-b-19921 #> x<-p->y: rs6430078 - Diastolic blood pressure, automated reading || id:ukb-b-7992 #> x<-p->y: rs8027450 - Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> x<-p->y: rs57866767 - Medication for cholesterol, blood pressure, diabetes, or take exogenous hormones: Blood pressure medication || id:ukb-b-18009 #> x<-p->y: rs10774625 - Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> x<-p->y: rs8027450 - Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> x<-p->y: rs57866767 - Diagnoses - secondary ICD10: I10 Essential (primary) hypertension || id:ukb-b-12493 #> p->y: rs10774625 - Treatment speciality of consultant (recoded): General medicine || id:ukb-b-12646 #> x<-p->y: rs8027450 - Treatment/medication code: atenolol || id:ukb-b-11632 #> x<-p->y: rs10774625 - Number of treatments/medications taken || id:ukb-b-3656 #> x<-p->y: rs9349379 - Treatment/medication code: ibuprofen || id:ukb-b-16866 #> x<-p->y: rs57866767 - Trunk fat-free mass || id:ukb-b-17409 #> x<-p->y: rs10774625 - Birth weight of first child || id:ukb-b-3357 #> x<-p->y: rs10774625 - Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> x<-p->y: rs57866767 - Vascular/heart problems diagnosed by doctor: None of the above || id:ukb-b-13352 #> x<-p->y: rs2681492 - Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> x<-p->y: rs10774625 - Non-cancer illness code, self-reported: hypertension || id:ukb-b-14057 #> x<-p->y: rs10774625 - Impedance of arm (right) || id:ukb-b-7859 #> p->y: rs9349379 - Operative procedures - main OPCS: K49.1 Percutaneous transluminal balloon angioplasty of one coronary artery || id:ukb-b-18018 #> x<-p->y: rs8027450 - Medication for cholesterol, blood pressure or diabetes: None of the above || id:ukb-b-12014 #> p->y: rs10774625 - Father's age at death || id:ukb-b-11303 #> x<-p->y: rs2681492 - Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> x<-p->y: rs10774625 - Vascular/heart problems diagnosed by doctor: High blood pressure || id:ukb-b-14177 #> x<-p->y: rs10774625 - Diastolic blood pressure, automated reading || id:ukb-b-7992 #> x<-p->y: rs8027450 - Diastolic blood pressure, automated reading || id:ukb-b-7992 #> x<-p->y: rs8027450 - Birth weight || id:ukb-b-13378 #> x<-p->y: rs57866767 - Trunk fat percentage || id:ukb-b-16407 #> p->y: rs10774625 - Illnesses of father: Heart disease || id:ukb-b-18408 #> p->y: rs9349379 - Illnesses of father: Heart disease || id:ukb-b-18408 #> x<-p->y: rs8027450 - Treatment/medication code: ramipril || id:ukb-b-11895 #> x<-p->y: rs9349379 - Vascular/heart problems diagnosed by doctor: Angina || id:ukb-b-8468 #> p->y: rs9349379 - Operation code: coronary artery bypass grafts (cabg) || id:ukb-b-12465 #> x<-p->y: rs2971603 - Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> x<-p->y: rs9349379 - Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> p->y: rs10774625 - Taking other prescription medications || id:ukb-b-20292 #> x<-p->y: rs8027450 - Age high blood pressure diagnosed || id:ukb-b-1061 #> x<-p->y: rs9349379 - Non-cancer illness code, self-reported: angina || id:ukb-b-8650 #> x<-p->y: rs10774625 - Treatment/medication code: bendroflumethiazide || id:ukb-b-18799 #> x<-p->y: rs8027450 - Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 #> p->y: rs10774625 - Non-cancer illness code, self-reported: heart attack/myocardial infarction || id:ukb-b-15829 #> p->y: rs9349379 - Treatment speciality of consultant (recoded): Cardiology || id:ukb-b-20300 #> x<-p->y: rs10774625 - Impedance of arm (left) || id:ukb-b-19379 #> x<-p->y: rs10774625 - Number of self-reported non-cancer illnesses || id:ukb-b-4063 #> p->y: rs9349379 - Diagnoses - main ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-1668 #> p->y: rs10774625 - Diagnoses - main ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-1668 #> p->y: rs7798197 - Diagnoses - main ICD10: I25.1 Atherosclerotic heart disease || id:ukb-b-1668 #> x<-p->y: rs57866767 - Trunk fat mass || id:ukb-b-20044 #> p->y: rs9349379 - Vascular/heart problems diagnosed by doctor: Heart attack || id:ukb-b-11590 #> x<-p->y: rs10774625 - Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> x<-p->y: rs8027450 - Medication for cholesterol, blood pressure or diabetes: Blood pressure medication || id:ukb-b-14395 #> x<-p->y: rs8027450 - Illnesses of mother: None of the above (group 1) || id:ukb-b-10454 #> x<-p->y: rs35114617 - Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 #> x<-p->y: rs10774625 - Interleukin-2 receptor subunit beta || id:prot-a-1519 #> p->y: rs9349379 - Myocardial infarction || id:ieu-a-798 #> p->y: rs10774625 - Myocardial infarction || id:ieu-a-798 #> p->y: rs10774625 - HDL cholesterol || id:ieu-a-299 #> x<-p->y: rs7798197 - Large vessel disease || id:ieu-a-1110 #> p->y: rs10774625 - Total cholesterol || id:ieu-a-301 #> p->y: rs2681492 - Myocardial infarction || id:ieu-a-798 #> p->y: rs10774625 - LDL cholesterol || id:ieu-a-300
This will estimate the outlier effect that is due to the candidate pathways, adjust the outlier-outcome estimate, and re-perform MR of exposure on outcome with the adjusted outliers.
By default, this adjusts for the trait that has the largest impact for a particular SNP.
There is also a multivariable adjustment method here, where for each outlier, all candidate trait effects are estimated jointly:
x$analyse.mv()
NOTE: it’s a good idea to check that there are no traits amongst the candidates that are identical or equivalent to the outcome:
id_remove = c("ieu-a-1110", "ieu-a-798", "ukb-b-1061", "ukb-b-10454", "ukb-b-1061", "ukb-b-11064", "ukb-b-11590", "ukb-b-11632", "ukb-b-11895", "ukb-b-11971", "ukb-b-12014", "ukb-b-12019", "ukb-b-12465", "ukb-b-12493", "ukb-b-13352", "ukb-b-13506", "ukb-b-12477", "ukb-b-12493", "ukb-b-12646", "ukb-b-13352", "ukb-b-13506", "ukb-b-14057", "ukb-b-14177", "ukb-b-14371", "ukb-b-14395", "ukb-b-15169", "ukb-b-15491", "ukb-b-15686", "ukb-b-15748", "ukb-b-15829", "ukb-b-16376", "ukb-b-16606", "ukb-b-1668", "ukb-b-17360", "ukb-b-18009", "ukb-b-18018", "ukb-b-18167", "ukb-b-18408", "ukb-b-18799", "ukb-b-20300", "ukb-b-20379", "ukb-b-3656", "ukb-b-4063", "ukb-b-7137", "ukb-b-7436", "ukb-b-7869", "ukb-b-7992", "ukb-b-8468", "ukb-b-8650", "ukb-b-8746", "ukb-b-9207", "ieu-a-1110", "ukb-b-1061", "ukb-b-11971", "ukb-b-12014", "ukb-b-12019", "ukb-b-19456", "ukb-b-8778", "ukb-b-10454", "ukb-b-11632", "ukb-b-11895") x$analyse.mv(id_remove = id_remove) #> Estimating joint effects of the following trait(s) associated with rs10774625 #> Birth weight || id:ukb-b-13378 #> Long-standing illness, disability or infirmity || id:ukb-b-13764 #> Treatment/medication code: aspirin || id:ukb-b-8755 #> Hip circumference || id:ukb-b-15590 #> Diagnoses - secondary ICD10: E03.9 Hypothyroidism, unspecified || id:ukb-b-4226 #> Standing height || id:ukb-b-10787 #> Weight || id:ukb-b-11842 #> Non-cancer illness code, self-reported: hypothyroidism/myxoedema || id:ukb-b-19732 #> Treatment/medication code: levothyroxine sodium || id:ukb-b-17918 #> Trunk fat-free mass || id:ukb-b-17409 #> Impedance of whole body || id:ukb-b-19921 #> Birth weight of first child || id:ukb-b-3357 #> Impedance of arm (right) || id:ukb-b-7859 #> Father's age at death || id:ukb-b-11303 #> Taking other prescription medications || id:ukb-b-20292 #> Impedance of arm (left) || id:ukb-b-19379 #> Interleukin-2 receptor subunit beta || id:prot-a-1519 #> HDL cholesterol || id:ieu-a-299 #> Total cholesterol || id:ieu-a-301 #> LDL cholesterol || id:ieu-a-300 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Birth weight || id:ukb-b-13378. Just keeping the first instance: #> rs2140240 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Hip circumference || id:ukb-b-15590. Just keeping the first instance: #> rs1294438 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Impedance of arm (right) || id:ukb-b-7859. Just keeping the first instance: #> rs111650620 #> rs1382568 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Standing height || id:ukb-b-10787. Just keeping the first instance: #> rs11252860 #> rs34773647 #> rs664317 #> rs7978217 #> rs11051456 #> rs1019075 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat-free mass || id:ukb-b-17409. Just keeping the first instance: #> rs3735352 #> rs3740591 #> rs1040457 #> Warning in format_data(d, type = "exposure", snps = NULL, phenotype_col = #> "phenotype", : eaf column is not numeric. Coercing... #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 4776 variants #> Removing 3745 of 4776 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 765 SNP(s) from 21 GWAS(s) #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs664317 #> rs11252860 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and HDL cholesterol || id:ieu-a-299 (ieu-a-299) #> Removing the following SNPs for incompatible alleles: #> rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs10498672, rs10499659, rs10505073, rs11122824, rs11664336, rs11756783, rs12258967, rs12572775, rs1290790, rs1420150, rs1467847, rs1556516, rs16905189, rs17010961, rs1867780, rs1875969, rs2138628, rs219162, rs2270894, rs2410728, rs2422054, rs2663335, rs2952615, rs3771382, rs3790086, rs3812163, rs4865956, rs519384, rs578475, rs6824592, rs7619139, rs7652177, rs7917801, rs7961994, rs832806, rs9352895, rs964184, rs968821 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and LDL cholesterol || id:ieu-a-300 (ieu-a-300) #> Removing the following SNPs for incompatible alleles: #> rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs10498672, rs10499659, rs10505073, rs11122824, rs11664336, rs11756783, rs12258967, rs12572775, rs1290790, rs1420150, rs1467847, rs1556516, rs16905189, rs17010961, rs1867780, rs1875969, rs2138628, rs219162, rs2270894, rs2410728, rs2422054, rs2663335, rs2952615, rs3771382, rs3790086, rs3812163, rs4865956, rs519384, rs578475, rs6824592, rs7619139, rs7652177, rs7917801, rs7961994, rs832806, rs9352895, rs964184, rs968821 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Total cholesterol || id:ieu-a-301 (ieu-a-301) #> Removing the following SNPs for incompatible alleles: #> rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs10498672, rs10499659, rs10505073, rs11122824, rs11664336, rs11756783, rs12258967, rs12572775, rs1290790, rs1420150, rs1467847, rs1556516, rs16905189, rs17010961, rs1867780, rs1875969, rs2138628, rs219162, rs2270894, rs2410728, rs2422054, rs2663335, rs2952615, rs3771382, rs3790086, rs3812163, rs4865956, rs519384, rs578475, rs6824592, rs7619139, rs7652177, rs7917801, rs7961994, rs832806, rs9352895, rs964184, rs968821 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Interleukin-2 receptor subunit beta || id:prot-a-1519 (prot-a-1519) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Standing height || id:ukb-b-10787 (ukb-b-10787) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Father's age at death || id:ukb-b-11303 (ukb-b-11303) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Weight || id:ukb-b-11842 (ukb-b-11842) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Birth weight || id:ukb-b-13378 (ukb-b-13378) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Long-standing illness, disability or infirmity || id:ukb-b-13764 (ukb-b-13764) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Hip circumference || id:ukb-b-15590 (ukb-b-15590) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Trunk fat-free mass || id:ukb-b-17409 (ukb-b-17409) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Treatment/medication code: levothyroxine sodium || id:ukb-b-17918 (ukb-b-17918) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of arm (left) || id:ukb-b-19379 (ukb-b-19379) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Non-cancer illness code, self-reported: hypothyroidism/myxoedema || id:ukb-b-19732 (ukb-b-19732) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of whole body || id:ukb-b-19921 (ukb-b-19921) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Taking other prescription medications || id:ukb-b-20292 (ukb-b-20292) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Birth weight of first child || id:ukb-b-3357 (ukb-b-3357) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Diagnoses - secondary ICD10: E03.9 Hypothyroidism, unspecified || id:ukb-b-4226 (ukb-b-4226) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of arm (right) || id:ukb-b-7859 (ukb-b-7859) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860, rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Treatment/medication code: aspirin || id:ukb-b-8755 (ukb-b-8755) #> Removing the following SNPs for incompatible alleles: #> rs664317, rs664317 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10228350, rs11664336, rs11756783, rs12572775, rs1290790, rs13264909, rs1467847, rs1556516, rs1580100, rs165656, rs3771382, rs3790086, rs3812163, rs418280, rs4243765, rs4302014, rs5759006, rs62134416, rs7652177, rs7754251, rs7917801, rs832806, rs9352895, rs9976812 #> Performing shrinkage #> After shrinkage keeping: #> ieu-a-299 #> ieu-a-300 #> prot-a-1519 #> ukb-b-10787 #> ukb-b-11303 #> ukb-b-11842 #> ukb-b-13378 #> ukb-b-13764 #> ukb-b-17918 #> ukb-b-19379 #> ukb-b-20175 #> ukb-b-20292 #> ukb-b-3357 #> ukb-b-4226 #> ukb-b-8755 #> Estimating joint effects of the following trait(s) associated with rs57866767 #> Impedance of arm (left) || id:ukb-b-19379 #> Impedance of whole body || id:ukb-b-19921 #> Arm fat percentage (left) || id:ukb-b-20188 #> Birth weight || id:ukb-b-13378 #> Leg fat percentage (left) || id:ukb-b-18377 #> Body fat percentage || id:ukb-b-8909 #> Leg fat percentage (right) || id:ukb-b-20531 #> Arm fat percentage (right) || id:ukb-b-12854 #> Impedance of arm (right) || id:ukb-b-7859 #> Trunk fat-free mass || id:ukb-b-17409 #> Trunk fat percentage || id:ukb-b-16407 #> Trunk fat mass || id:ukb-b-20044 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Arm fat percentage (left) || id:ukb-b-20188. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Birth weight || id:ukb-b-13378. Just keeping the first instance: #> rs2140240 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Body fat percentage || id:ukb-b-8909. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Impedance of arm (right) || id:ukb-b-7859. Just keeping the first instance: #> rs111650620 #> rs1382568 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat percentage (left) || id:ukb-b-18377. Just keeping the first instance: #> rs1428 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Leg fat percentage (right) || id:ukb-b-20531. Just keeping the first instance: #> rs7027096 #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat mass || id:ukb-b-20044. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat percentage || id:ukb-b-16407. Just keeping the first instance: #> rs2731238 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Trunk fat-free mass || id:ukb-b-17409. Just keeping the first instance: #> rs3735352 #> rs3740591 #> rs1040457 #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 5198 variants #> Removing 4002 of 5198 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 668 SNP(s) from 13 GWAS(s) #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs2731238 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Arm fat percentage (right) || id:ukb-b-12854 (ukb-b-12854) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Birth weight || id:ukb-b-13378 (ukb-b-13378) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Trunk fat percentage || id:ukb-b-16407 (ukb-b-16407) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Trunk fat-free mass || id:ukb-b-17409 (ukb-b-17409) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Leg fat percentage (left) || id:ukb-b-18377 (ukb-b-18377) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of arm (left) || id:ukb-b-19379 (ukb-b-19379) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of whole body || id:ukb-b-19921 (ukb-b-19921) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Trunk fat mass || id:ukb-b-20044 (ukb-b-20044) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Arm fat percentage (left) || id:ukb-b-20188 (ukb-b-20188) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Leg fat percentage (right) || id:ukb-b-20531 (ukb-b-20531) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Impedance of arm (right) || id:ukb-b-7859 (ukb-b-7859) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Body fat percentage || id:ukb-b-8909 (ukb-b-8909) #> Removing the following SNPs for incompatible alleles: #> rs2731238, rs2731238 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs1080347, rs10887578, rs11208779, rs12722976, rs13264909, rs1443641, rs1905095, rs2592828, rs28721380, rs2968669, rs3771382, rs3773851, rs445077, rs4714935, rs59086897, rs62134416, rs6540497, rs7491529, rs7788672, rs7917801, rs7971536, rs9882731, rs9976812 #> Performing shrinkage #> After shrinkage keeping: #> ukb-b-12854 #> ukb-b-13378 #> ukb-b-17409 #> ukb-b-20175 #> ukb-b-20188 #> ukb-b-20531 #> ukb-b-7859 #> Estimating joint effects of the following trait(s) associated with rs35114617 #> Sitting height || id:ukb-b-16881 #> Standing height || id:ukb-b-10787 #> Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Sitting height || id:ukb-b-16881. Just keeping the first instance: #> rs4651157 #> rs872937 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Standing height || id:ukb-b-10787. Just keeping the first instance: #> rs11252860 #> rs34773647 #> rs664317 #> rs7978217 #> rs11051456 #> rs1019075 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 1620 variants #> Removing 796 of 1620 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 738 SNP(s) from 4 GWAS(s) #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs11252860 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Glutaminyl-peptide cyclotransferase-like protein || id:prot-a-2466 (prot-a-2466) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10811092, rs12572775, rs12722976, rs1290790, rs1467847, rs153661, rs3771382, rs3790086, rs3812163, rs418280, rs4302014, rs6947915, rs7652177, rs7847059, rs832806, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Standing height || id:ukb-b-10787 (ukb-b-10787) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10811092, rs12572775, rs12722976, rs1290790, rs1467847, rs153661, rs3771382, rs3790086, rs3812163, rs418280, rs4302014, rs6947915, rs7652177, rs7847059, rs832806, rs9976812 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Sitting height || id:ukb-b-16881 (ukb-b-16881) #> Removing the following SNPs for incompatible alleles: #> rs11252860, rs11252860 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs10811092, rs12572775, rs12722976, rs1290790, rs1467847, rs153661, rs3771382, rs3790086, rs3812163, rs418280, rs4302014, rs6947915, rs7652177, rs7847059, rs832806, rs9976812 #> Performing shrinkage #> After shrinkage keeping: #> ukb-b-10787 #> ukb-b-20175 #> Estimating joint effects of the following trait(s) associated with rs8027450 #> Birth weight of first child || id:ukb-b-3357 #> Birth weight || id:ukb-b-13378 #> Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Birth weight || id:ukb-b-13378. Just keeping the first instance: #> rs2140240 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 507 variants #> Removing 183 of 507 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 318 SNP(s) from 4 GWAS(s) #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Medication for cholesterol, blood pressure or diabetes: Cholesterol lowering medication || id:ukb-b-11740 (ukb-b-11740) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs1344672, rs2246832 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Birth weight || id:ukb-b-13378 (ukb-b-13378) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs1344672, rs2246832 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Birth weight of first child || id:ukb-b-3357 (ukb-b-3357) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs1344672, rs2246832 #> Performing shrinkage #> After shrinkage keeping: #> ukb-b-11740 #> ukb-b-13378 #> ukb-b-20175 #> ukb-b-3357 #> Estimating joint effects of the following trait(s) associated with rs9349379 #> Operative procedures - secondary OPCS: Y02.2 Insertion of prosthesis into organ NOC || id:ukb-b-1744 #> Treatment/medication code: ibuprofen || id:ukb-b-16866 #> Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Pain type(s) experienced in last month: Headache || id:ukb-b-12181. Just keeping the first instance: #> rs34555420 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 298 variants #> Removing 36 of 298 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 259 SNP(s) from 4 GWAS(s) #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Pain type(s) experienced in last month: Headache || id:ukb-b-12181 (ukb-b-12181) #> Removing the following SNPs for incompatible alleles: #> rs17811915, rs17811915 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs2246832 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Treatment/medication code: ibuprofen || id:ukb-b-16866 (ukb-b-16866) #> Removing the following SNPs for incompatible alleles: #> rs17811915, rs17811915 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs2246832 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Operative procedures - secondary OPCS: Y02.2 Insertion of prosthesis into organ NOC || id:ukb-b-1744 (ukb-b-1744) #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs2246832 #> Performing shrinkage #> After shrinkage keeping: #> ukb-b-12181 #> ukb-b-1744 #> ukb-b-20175 #> Estimating joint effects of the following trait(s) associated with rs2971603 #> Pain type(s) experienced in last month: Headache || id:ukb-b-12181 #> Only one candidate trait for SNP rs2971603 so performing standard MVMR instead of LASSO #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Pain type(s) experienced in last month: Headache || id:ukb-b-12181. Just keeping the first instance: #> rs34555420 #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Warning: 'clump_data' is deprecated. #> Use 'ieugwasr::ld_clump()' instead. #> See help("Deprecated") #> Clumping 1, 292 variants #> Removing 34 of 292 variants due to LD with other variants or absence from LD reference panel #> Extracting data for 257 SNP(s) from 2 GWAS(s) #> Warning in .fun(piece, ...): Duplicated SNPs present in exposure data for phenotype 'Systolic blood pressure, automated reading || id:ukb-b-20175. Just keeping the first instance: #> rs17811915 #> Harmonising Systolic blood pressure, automated reading || id:ukb-b-20175 (ukb-b-20175) and Pain type(s) experienced in last month: Headache || id:ukb-b-12181 (ukb-b-12181) #> Removing the following SNPs for incompatible alleles: #> rs17811915, rs17811915 #> Removing the following SNPs for being palindromic with intermediate allele frequencies: #> rs11592442, rs12779675, rs1290790, rs2246832
The adjusted effect estimates:
x$output$analyse.mv$estimates #> est b se pval nsnp Q #> 1 Raw 0.5991067 0.07717696 2.642311e-13 233 870.8370 #> 2 Outliers removed (all) 0.6437695 0.06349886 3.767303e-20 222 393.1945 #> 3 Outliers removed (candidates) 0.7095277 0.05475819 6.135623e-29 227 553.3497 #> 4 Outliers adjusted 0.6192846 0.06555078 3.930161e-18 233 616.0294 #> int Isq #> 1 0 0.7312930 #> 2 0 0.4328507 #> 3 0 0.5879640 #> 4 0 0.6201480
Visualisation
Adjustment plot
A plot is generated showing how SNP effects have changed due to candidate trait adjustments in:
x$output$analyse.mv$plot
Network plot
To produce a basic diagram of the connectivity of SNPs, candidate traits, exposure and outcome:
tryx.network(x$output)
This shows that some candidate traits influence the exposure only, the outcome only, or both the exposure and the outcome.
Volcano plot
You can also create a volcano plot of the candidate-exposure and/or candidate-outcome associations. e.g. to show exposures and outcomes
volcano_plot( rbind(x$output$candidate_exposure_mr, x$output$candidate_outcome_mr) )
or e.g. just exposures
volcano_plot(x$output$candidate_exposure_mr)
