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snp_PRS

PRS

Description

Polygenic Risk Scores with possible clumping and thresholding.

Usage

snp_PRS(
  G,
  betas.keep,
  ind.test = rows_along(G),
  ind.keep = cols_along(G),
  same.keep = rep(TRUE, length(ind.keep)),
  lpS.keep = NULL,
  thr.list = 0
)

Arguments

G

A FBM.code256 (typically <bigSNP>$genotypes).
You shouldn't have missing values. Also, remember to do quality control, e.g. some algorithms in this package won't work if you use SNPs with 0 MAF.
betas.keep

Numeric vector of weights associated with each SNP corresponding to ind.keep. You may want to see big_univLinReg or big_univLogReg.
ind.test

The individuals on whom to project the scores. Default uses all.
ind.keep

Column (SNP) indices to use (if using clumping, the output of snp_clumping). Default doesn't clump.
same.keep

A logical vector associated with betas.keep whether the reference allele is the same for G. Default is all TRUE (for example when you train the betas on the same dataset). Otherwise, use same_ref.
lpS.keep

Numeric vector of -log10(p-value) associated with betas.keep. Default doesn't use thresholding.
thr.list

Threshold vector on lpS.keep at which SNPs are excluded if they are not significant enough. Default doesn't use thresholding.

Value

A matrix of scores, where rows correspond to ind.test and columns correspond to thr.list.

Examples

test <- snp_attachExtdata()
G <- big_copy(test$genotypes, ind.col = 1:1000)
CHR <- test$map$chromosome[1:1000]
POS <- test$map$physical.position[1:1000]
y01 <- test$fam$affection - 1

# PCA -> covariables
obj.svd <- snp_autoSVD(G, infos.chr = CHR, infos.pos = POS)

# train and test set
ind.train <- sort(sample(nrow(G), 400))
ind.test <- setdiff(rows_along(G), ind.train) # 117

# GWAS
gwas.train <- big_univLogReg(G, y01.train = y01[ind.train],
                             ind.train = ind.train,
                             covar.train = obj.svd$u[ind.train, ])
# clumping
ind.keep <- snp_clumping(G, infos.chr = CHR,
                         ind.row = ind.train,
                         S = abs(gwas.train$score))
# -log10(p-values) and thresolding
summary(lpS.keep <- -predict(gwas.train)[ind.keep])
thrs <- seq(0, 4, by = 0.5)
nb.pred <- sapply(thrs, function(thr) sum(lpS.keep > thr))

# PRS
prs <- snp_PRS(G, betas.keep = gwas.train$estim[ind.keep],
               ind.test = ind.test,
               ind.keep = ind.keep,
               lpS.keep = lpS.keep,
               thr.list = thrs)

# AUC as a function of the number of predictors
aucs <- apply(prs, 2, AUC, target = y01[ind.test])
library(ggplot2)
qplot(nb.pred, aucs) +
  geom_line() +
  scale_x_log10(breaks = nb.pred) +
  labs(x = "Number of predictors", y = "AUC") +
  theme_bigstatsr()
bigsnpr

Analysis of Massive SNP Arrays

v1.10.8
GPL-3
Authors
Florian Privé [aut, cre], Michael Blum [ths], Hugues Aschard [ths], Bjarni Jóhann Vilhjálmsson [ths]
Initial release
2022-07-05

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