Last updated: 2023-12-07

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Load packages and functions

library(ctwas)
library(data.table)
library(tidyverse)

LDL

  • LDL GWAS and LD reference panel are both from UKBB.
  • Select one locus in chr22.
  • Randomly changed the z-scores for 100 variants (50 with abs(z) > 2 and 50 with abs(z) < 2).
  • Randomly flipped the z-scores for 20 variants (10 with abs(z) > 2 and 10 with abs(z) < 2).
  • Run DENTIST on the GWAS sumstats of the locus, with 2Mb vs. 1Mb window, or 1 iteration vs. 10 iterations.
trait <- "LDL"

LD Regions (ldetect blocks)

regions <- system.file("extdata/ldetect", "EUR.b38.bed", package = "ctwas")
regions_df <- read.table(regions, header = T)
regions_df <- regions_df %>% dplyr::arrange(chr, start, stop) %>% dplyr::mutate(locus = 1:nrow(regions_df))

Locus 950

locus = "950"
outdir <- paste0("/project2/xinhe/shared_data/multigroup_ctwas/ld_mismatch_test/", trait)
sumstats_hg38_locus <- readRDS(file.path(outdir, paste0(trait, ".test.locus", locus,".changed.sumstats.rds")))

region_df <- regions_df[regions_df$locus == locus,]
print(region_df)

locus_df <- sumstats_hg38_locus
#       chr    start     stop locus
# 950 chr22 24588236 26395662   950

Load Allele Frequency

CHR=22
dentist.dir <- paste0("/project2/xinhe/shared_data/multigroup_ctwas/DENTIST/", trait)
dentist.freq.df <- data.table::fread(file.path(dentist.dir, paste0("LDL-ukb-d-30780_irnt.ukb_chr", CHR, ".b38.frq")))

locus_df$Freq_A1 <- dentist.freq.df$Freq_A1[match(locus_df$snp, dentist.freq.df$RS_ID)]
locus_df$MAF <- pmin(locus_df$Freq_A1, 1-locus_df$Freq_A1)

SuSiE result

susie_original_res <- readRDS(file.path(outdir, paste0(trait, ".test.locus", locus,".original.condz.dist.rds")))
susie_new_res <- readRDS(file.path(outdir, paste0(trait, ".test.locus", locus,".changed.condz.dist.rds")))

stopifnot(all.equal(locus_df$snp, susie_original_res$id))
stopifnot(all.equal(locus_df$snp, susie_new_res$id))

locus_df$susie_original_LP <- -log10(susie_original_res$p_diff)
locus_df$susie_original_logLR <- susie_original_res$logLR

locus_df$susie_new_LP <- -log10(susie_new_res$p_diff)
locus_df$susie_new_logLR <- susie_new_res$logLR

DENTIST result

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".original.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_original_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".original.10iters.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_original_10iters_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".original.1Mb.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_original_1Mb_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".original.1Mb.10iters.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_original_1Mb_10iters_LP <- dentist_res$LP[m]
dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".changed.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_new_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".changed.10iters.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_new_10iters_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".changed.1Mb.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_new_1Mb_LP <- dentist_res$LP[m]

dentist_res <- data.table::fread(file.path(outdir, paste0(trait, ".test.locus", locus, ".changed.1Mb.10iters.DENTIST.full.txt")))
colnames(dentist_res) <- c("rsID", "chisq", "LP", "ifDup")
m <- match(locus_df$snp, dentist_res$rsID)
locus_df$dentist_new_1Mb_10iters_LP <- dentist_res$LP[m]

DENTIST vs. SuSiE on original data

p1 <- ggplot(na.omit(locus_df), aes(x = dentist_original_10iters_LP, y = susie_original_LP)) +
  geom_point(alpha=0.6) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST original 2Mb window -log10P", y = "SuSiE original -log10P", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p2 <- ggplot(na.omit(locus_df), aes(x = dentist_original_1Mb_10iters_LP, y = susie_original_LP)) +
  geom_point(alpha=0.6) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST original 1Mb window -log10P", y = "SuSiE original -log10P", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p3 <- ggplot(na.omit(locus_df), aes(x = dentist_original_10iters_LP, y = dentist_original_LP)) +
  geom_point(alpha=0.6) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST original 2Mb window 10 iterations -log10P", 
       y = "DENTIST original 2Mb window 1 iteration -log10P", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p4 <- ggplot(na.omit(locus_df), aes(x = dentist_original_1Mb_10iters_LP, y = dentist_original_1Mb_LP)) +
  geom_point(alpha=0.6) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST original 2Mb window 10 iterations -log10P", 
       y = "DENTIST original 2Mb window 1 iteration -log10P", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

cowplot::plot_grid(p1, p2, p3, p4, 
                   labels = c('A', 'B', 'C', 'D'),
                   align="hv")
# Warning: Removed 1 rows containing missing values (`geom_point()`).
# Removed 1 rows containing missing values (`geom_point()`).

Version Author Date
78e8869 kevinlkx 2023-12-07

DENTIST 1 iteration vs. 10 iterations, 1Mb vs. 2Mb window

p1 <- ggplot(na.omit(locus_df), aes(x = dentist_new_LP, y = dentist_new_10iters_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 2Mb window 1 iterations -log10P", 
       y = "DENTIST 2Mb window 10 iteration -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p2 <- ggplot(na.omit(locus_df), aes(x = dentist_new_1Mb_LP, y = dentist_new_1Mb_10iters_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 1Mb window 1 iterations -log10P", 
       y = "DENTIST 1Mb window 10 iteration -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p3 <- ggplot(na.omit(locus_df), aes(x = dentist_new_LP, y = dentist_new_1Mb_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 2Mb window 1iteration -log10P", 
       y = "DENTIST 1Mb window 1iteration -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p4 <- ggplot(na.omit(locus_df), aes(x = dentist_new_10iters_LP, y = dentist_new_1Mb_10iters_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 2Mb window 10 iterations -log10P", 
       y = "DENTIST 1Mb window 10 iterations -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

cowplot::plot_grid(p1, p2, p3, p4, 
                   labels = c('A', 'B', 'C', 'D'),
                   align="hv")
# Warning: Removed 2 rows containing missing values (`geom_point()`).
# Warning: Removed 1 rows containing missing values (`geom_point()`).
# Removed 1 rows containing missing values (`geom_point()`).
# Warning: Removed 2 rows containing missing values (`geom_point()`).

Version Author Date
78e8869 kevinlkx 2023-12-07

DENTIST vs. SuSiE RSS

p1 <- ggplot(na.omit(locus_df), aes(x = dentist_new_LP, y = susie_new_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 2Mb window 1 iteration -log10P", y = "SuSiE -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p2 <- ggplot(na.omit(locus_df), aes(x = dentist_new_1Mb_LP, y = susie_new_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 1Mb window 1 iteration -log10P", y = "SuSiE -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p3 <- ggplot(na.omit(locus_df), aes(x = dentist_new_10iters_LP, y = susie_new_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 2Mb window 10 iterations -log10P", y = "SuSiE -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

p4 <- ggplot(na.omit(locus_df), aes(x = dentist_new_1Mb_10iters_LP, y = susie_new_LP, col = factor(changed))) +
  geom_point(alpha=0.6) +
  scale_colour_manual(values = c("0" = "black", "1" = "red")) +
  xlim(0, 100) + ylim(0, 100) +
  labs(x = "DENTIST 1Mb window 10 iterations -log10P", y = "SuSiE -log10P", 
       color = "Mismatch", 
       title = paste0(trait, " locus", locus)) +
  geom_abline(intercept = 0, slope = 1) + 
  geom_vline(xintercept = -log10(5e-8), col = "red") +
  geom_hline(yintercept = -log10(5e-8), col = "red") +
  theme_bw()

cowplot::plot_grid(p1, p2, p3, p4, 
                   labels = c('A', 'B', 'C', 'D'),
                   align="hv")
# Warning: Removed 2 rows containing missing values (`geom_point()`).
# Removed 2 rows containing missing values (`geom_point()`).
# Removed 2 rows containing missing values (`geom_point()`).
# Removed 2 rows containing missing values (`geom_point()`).

Version Author Date
78e8869 kevinlkx 2023-12-07 

sessionInfo()
# R version 4.2.0 (2022-04-22)
# Platform: x86_64-pc-linux-gnu (64-bit)
# Running under: CentOS Linux 7 (Core)
# 
# Matrix products: default
# BLAS/LAPACK: /software/openblas-0.3.13-el7-x86_64/lib/libopenblas_haswellp-r0.3.13.so
# 
# locale:
#  [1] LC_CTYPE=en_US.UTF-8 LC_NUMERIC=C         LC_TIME=C           
#  [4] LC_COLLATE=C         LC_MONETARY=C        LC_MESSAGES=C       
#  [7] LC_PAPER=C           LC_NAME=C            LC_ADDRESS=C        
# [10] LC_TELEPHONE=C       LC_MEASUREMENT=C     LC_IDENTIFICATION=C 
# 
# attached base packages:
# [1] stats     graphics  grDevices utils     datasets  methods   base     
# 
# other attached packages:
#  [1] forcats_1.0.0     stringr_1.5.0     dplyr_1.1.0       purrr_1.0.1      
#  [5] readr_2.1.4       tidyr_1.3.0       tibble_3.1.8      ggplot2_3.4.1    
#  [9] tidyverse_1.3.2   data.table_1.14.6 ctwas_0.1.35      workflowr_1.7.0  
# 
# loaded via a namespace (and not attached):
#  [1] httr_1.4.4          sass_0.4.5          jsonlite_1.8.4     
#  [4] foreach_1.5.2       pgenlibr_0.3.3      logging_0.10-108   
#  [7] modelr_0.1.10       bslib_0.4.2         assertthat_0.2.1   
# [10] getPass_0.2-2       highr_0.10          googlesheets4_1.0.1
# [13] cellranger_1.1.0    yaml_2.3.7          pillar_1.8.1       
# [16] backports_1.4.1     lattice_0.20-45     glue_1.6.2         
# [19] digest_0.6.31       promises_1.2.0.1    rvest_1.0.3        
# [22] colorspace_2.1-0    cowplot_1.1.1       htmltools_0.5.4    
# [25] httpuv_1.6.5        Matrix_1.5-3        pkgconfig_2.0.3    
# [28] broom_1.0.3         haven_2.5.1         scales_1.2.1       
# [31] processx_3.8.0      whisker_0.4         later_1.3.0        
# [34] tzdb_0.3.0          timechange_0.2.0    git2r_0.30.1       
# [37] googledrive_2.0.0   farver_2.1.1        generics_0.1.3     
# [40] ellipsis_0.3.2      cachem_1.0.6        withr_2.5.0        
# [43] cli_3.6.0           crayon_1.5.2        magrittr_2.0.3     
# [46] readxl_1.4.2        evaluate_0.20       ps_1.7.2           
# [49] fs_1.6.1            fansi_1.0.4         xml2_1.3.3         
# [52] tools_4.2.0         hms_1.1.2           gargle_1.3.0       
# [55] lifecycle_1.0.3     munsell_0.5.0       reprex_2.0.2       
# [58] callr_3.7.3         compiler_4.2.0      jquerylib_0.1.4    
# [61] rlang_1.0.6         grid_4.2.0          iterators_1.0.14   
# [64] rstudioapi_0.14     labeling_0.4.2      rmarkdown_2.20     
# [67] gtable_0.3.1        codetools_0.2-18    DBI_1.1.3          
# [70] R6_2.5.1            lubridate_1.9.2     knitr_1.42         
# [73] fastmap_1.1.0       utf8_1.2.3          rprojroot_2.0.3    
# [76] stringi_1.7.12      Rcpp_1.0.10         vctrs_0.5.2        
# [79] dbplyr_2.3.0        tidyselect_1.2.0    xfun_0.37