fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS

• DOI: 10.1186/s12859-022-04838-0
• Publication Date: 2022-07-30T09:02:52Z
• Authors: Anna Hutchinson; James Liley; Chris Wallace
• Keywords: 0301 basic medicine; 0303 health sciences; Genome; QH301-705.5; Computer applications to medicine. Medical informatics; R858-859.7; Functional genomics; Genomics; Polymorphism, Single Nucleotide; FDR; 03 medical and health sciences; Diabetes Mellitus, Type 1; Power; Humans; GWAS; Multiple testing; Biology (General); Software; Genome-Wide Association Study

AbstractBackgroundGenome-wide association studies (GWAS) are limited in power to detect associations that exceed the stringent genome-wide significance threshold. This limitation can be alleviated by leveraging relevant auxiliary data, such as functional genomic data. Frameworks utilising the conditional false discovery rate have been developed for this purpose, and have been shown to increase power for GWAS discovery whilst controlling the false discovery rate. However, the methods are currently only applicable for continuous auxiliary data and cannot be used to leverage auxiliary data with a binary representation, such as whether SNPs are synonymous or non-synonymous, or whether they reside in regions of the genome with specific activity states.ResultsWe describe an extension to the cFDR framework for binary auxiliary data, called “Binary cFDR”. We demonstrate FDR control of our method using detailed simulations, and show that Binary cFDR performs better than a comparator method in terms of sensitivity and FDR control. We introduce an all-encompassing user-oriented CRAN R package (https://annahutch.github.io/fcfdr/;https://cran.r-project.org/web/packages/fcfdr/index.html) and demonstrate its utility in an application to type 1 diabetes, where we identify additional genetic associations.ConclusionsOur all-encompassing R package, , serves as a comprehensive toolkit to unite GWAS and functional genomic data in order to increase statistical power to detect genetic associations.