Last updated: 2022-06-08
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Knit directory: finemap/analysis/
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In this small example drawn from our simulations, we show that that FINEMAP works well with an “in-sample LD” matrix—that is, a correlation matrix that was estimated using the same sample that was used to compute the single-SNP association statistics—but, can perform surprisingly poorly with an “out-of-sample” LD matrix. We have observed that this degradation in performance only occurs in rare cases, specifically when the effects of the causal SNPs are very large–i.e., when individual SNPs explain a large fraction of the total variance in the phenotype. So in this example the phenotypes were simulated with large coefficients for the causal SNPs.
We also run SuSiE on the same data. Unlike FINEMAP, SuSiE performs similarly well with both the in-sample and out-of-sample LD matrix.
First, we load some packages used in the code below.
library(data.table)
library(susieR)
library(ggplot2)
library(cowplot)
Load the summary data, the least-squares effect estimates \(\hat{\beta}_i\) and their standard errors \(\hat{s}_i\). Here weq also compute the z-scores since SuSiE accepts the z-scores as input.
dat1 <- readRDS("../data/small_data_11.rds")
dat3 <- readRDS("../data/small_data_11_sim_gaussian_pve_n_8_get_sumstats_n_1.rds")
maf <- dat1$maf$in_sample
bhat <- dat3$sumstats$bhat
shat <- dat3$sumstats$shat
z <- bhat/shat
In this simulation, two of the SNPs have a nonzero effect on the phenotype:
dat2 <- readRDS("../data/small_data_11_sim_gaussian_pve_n_8.rds")
b <- drop(dat2$meta$true_coef)
cat("True causal SNPs:\n")
which(b != 0)
# True causal SNPs:
# [1] 305 740
sessionInfo()
# R version 3.6.2 (2019-12-12)
# Platform: x86_64-apple-darwin15.6.0 (64-bit)
# Running under: macOS Catalina 10.15.7
#
# Matrix products: default
# BLAS: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
# LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.dylib
#
# locale:
# [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
#
# attached base packages:
# [1] stats graphics grDevices utils datasets methods base
#
# other attached packages:
# [1] cowplot_1.0.0 ggplot2_3.3.5 susieR_0.12.07 data.table_1.12.8
#
# loaded via a namespace (and not attached):
# [1] tidyselect_1.1.1 xfun_0.29 bslib_0.3.1 purrr_0.3.4
# [5] lattice_0.20-38 colorspace_1.4-1 vctrs_0.3.8 generics_0.0.2
# [9] htmltools_0.5.2 yaml_2.2.0 utf8_1.1.4 rlang_0.4.11
# [13] mixsqp_0.3-46 jquerylib_0.1.4 later_1.0.0 pillar_1.6.2
# [17] withr_2.5.0 DBI_1.1.0 glue_1.4.2 plyr_1.8.5
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# [25] gtable_0.3.0 workflowr_1.7.0 evaluate_0.14 knitr_1.37
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# [37] promises_1.1.0 backports_1.1.5 scales_1.1.0 jsonlite_1.7.2
# [41] fs_1.5.2 digest_0.6.23 stringi_1.4.3 processx_3.5.2
# [45] dplyr_1.0.7 rprojroot_1.3-2 grid_3.6.2 tools_3.6.2
# [49] magrittr_2.0.1 sass_0.4.0 tibble_3.1.3 crayon_1.4.1
# [53] whisker_0.4 pkgconfig_2.0.3 ellipsis_0.3.2 Matrix_1.2-18
# [57] reshape_0.8.8 assertthat_0.2.1 rmarkdown_2.11 rstudioapi_0.13
# [61] R6_2.4.1 git2r_0.29.0 compiler_3.6.2