BR_ss: Bootstrap method for use with discovery GWAS

In amandaforde/winnerscurse: Winner's Curse Adjustment Methods for Summary Statistics from Genome-Wide Association Studies

Bootstrap method for use with discovery GWAS

Description

BR_ss is a function which aims to use summary statistics to alleviate Winner's Curse bias in SNP-trait association estimates, obtained from a discovery GWAS. The function implements a parametric bootstrap approach, proposed by Forde et al. (2023). This approach was inspired by the bootstrap resampling method detailed in Faye et al. (2011), which requires original individual-level data.

Usage

BR_ss(summary_data, seed_opt = FALSE, seed = 1998)

Arguments

summary_data	A data frame containing summary statistics from the discovery GWAS. It must have three columns with column names rsid, beta and se, respectively, and columns beta and se must contain numerical values. Each row must correspond to a unique SNP, identified by rsid. The function requires that there must be at least 5 SNPs as any less will result in issues upon usage of the smoothing spline.
seed_opt	A logical value which allows the user to choose if they wish to set a seed, in order to ensure reproducibility of adjusted estimates. Small differences can occur between iterations of the function with the same data set due to the use of parametric bootstrapping. The default setting is seed_opt=FALSE.
seed	A numerical value which specifies the seed used if seed_opt=TRUE. The default setting is the arbitrary value of 1998.

Value

A data frame with the inputted summary data occupying the first three columns. The new adjusted association estimates for each SNP are returned in the fourth column, namely beta_BR_ss. The SNPs are contained in this data frame according to their significance, with the most significant SNP, i.e. the SNP with the largest absolute z-statistic, now located in the first row of the data frame.

References

Forde, A., Hemani, G., & Ferguson, J. (2023). Review and further developments in statistical corrections for Winner’s Curse in genetic association studies. PLoS Genetics, 19(9), e1010546.

See Also

https://amandaforde.github.io/winnerscurse/articles/winners_curse_methods.html for illustration of the use of BR_ss with a toy data set and further information regarding the computation of the adjusted SNP-trait association estimates.

amandaforde/winnerscurse documentation built on March 9, 2024, 6:09 p.m.