MR type 1 error rate
One instrument for X and X has no influence on Y
TwoSampleMR version 0.5.6
[>] New: Option to use non-European LD reference panels for clumping etc
[>] Some studies temporarily quarantined to verify effect allele
[>] See news(package='TwoSampleMR') and https://gwas.mrcieu.ac.uk for further details
Attaching package: 'simulateGP'
The following objects are masked from 'package:TwoSampleMR':
allele_frequency, contingency, get_population_allele_frequency
Attaching package: 'dplyr'
The following objects are masked from 'package:stats':
filter, lag
The following objects are masked from 'package:base':
intersect, setdiff, setequal, union
set.seed (12345 )
map <- tibble (snp= 1 , af= 0.5 )
params_x <- generate_gwas_params (map= map, h2= 0.01 , S= - 0.4 , Pi= 1 )
params_y <- generate_gwas_params (map= map, h2= 0.0 , S= - 0.4 , Pi= 1 )
nid <- 100000
ss <- summary_set (
beta_gx= params_x$ beta,
beta_gy= params_y$ beta,
af= params_x$ af,
n_gx= 10000 ,
n_gy= 10000 ,
n_overlap= 0 ,
cor_xy= 0.5
)
Perform MR with single causal variant
Rows: 1
Columns: 9
$ id.exposure <chr> "X"
$ id.outcome <chr> "Y"
$ outcome <chr> "Y"
$ exposure <chr> "X"
$ method <chr> "Wald ratio"
$ nsnp <dbl> 1
$ b <dbl> -0.08648138
$ se <dbl> 0.0892847
$ pval <dbl> 0.3327436
Perform MR with causal variant + 100 correlated tag SNPs
ss2 <- ss[rep (1 ,100 ),] %>% mutate (SNP= 1 : 100 )
mr (ss2, method_list= "mr_ivw" ) %>% glimpse ()
Rows: 1
Columns: 9
$ id.exposure <chr> "X"
$ id.outcome <chr> "Y"
$ outcome <chr> "Y"
$ exposure <chr> "X"
$ method <chr> "Inverse variance weighted"
$ nsnp <int> 100
$ b <dbl> -0.08648138
$ se <dbl> 0.00892847
$ pval <dbl> 3.457243e-22
Very small p-value - inflated type 1 error
Checking
n <- 10000
nsnp <- 10
g <- matrix (0 , n, nsnp)
g[,1 ] <- rnorm (n)
for (i in 2 : nsnp)
{
g[,i] <- g[,i] + rnorm (n, sd= 0.5 )
}
y <- g[,1 ] + rnorm (n)
grs <- rowSums (g)
cov (y, grs)
R version 4.2.1 Patched (2022-09-06 r82817)
Platform: aarch64-apple-darwin20 (64-bit)
Running under: macOS Monterey 12.6
Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRlapack.dylib
locale:
[1] en_GB.UTF-8/en_GB.UTF-8/en_GB.UTF-8/C/en_GB.UTF-8/en_GB.UTF-8
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] dplyr_1.0.10 simulateGP_0.1.2 TwoSampleMR_0.5.6
loaded via a namespace (and not attached):
[1] Rcpp_1.0.9 plyr_1.8.7 compiler_4.2.1 pillar_1.8.1
[5] iterators_1.0.14 tools_4.2.1 mr.raps_0.2 digest_0.6.29
[9] jsonlite_1.8.0 evaluate_0.16 lifecycle_1.0.3 tibble_3.1.8
[13] lattice_0.20-45 pkgconfig_2.0.3 rlang_1.0.6 Matrix_1.4-1
[17] foreach_1.5.2 DBI_1.1.3 cli_3.4.1 yaml_2.3.5
[21] xfun_0.33 fastmap_1.1.0 stringr_1.4.1 knitr_1.40
[25] generics_0.1.3 htmlwidgets_1.5.4 vctrs_0.5.1 tidyselect_1.1.2
[29] glmnet_4.1-4 grid_4.2.1 nortest_1.0-4 glue_1.6.2
[33] R6_2.5.1 fansi_1.0.3 survival_3.4-0 rmarkdown_2.16
[37] purrr_0.3.4 magrittr_2.0.3 ellipsis_0.3.2 codetools_0.2-18
[41] htmltools_0.5.3 splines_4.2.1 assertthat_0.2.1 shape_1.4.6
[45] utf8_1.2.2 stringi_1.7.8