Multi-SNP mediation intersection-union test

• DOI: 10.1093/bioinformatics/btz285
• Publication Date: 2019-04-16T19:22:31Z
• Authors: Wujuan Zhong; Cassandra N Sprac...; Karen L Mohlke; Xiaojing Zheng; Jason Fine; Yun Li
• Keywords: Smut; SNP; Genome-wide Association Study; R package

Tens of thousands reproducibly identified GWAS (Genome-Wide Association Studies) variants, with the vast majority falling in non-coding regions resulting no eventual protein products, call urgently for mechanistic interpretations. Although numerous methods exist, there are few, if any methods, simultaneously testing mediation effects multiple correlated SNPs via some mediator (e.g. expression a gene neighborhood) on phenotypic outcome. We propose multi-SNP intersection-union test (SMUT) to fill this methodological gap. Our extensive simulations demonstrate validity SMUT as well substantial, up 92%, power gains over alternative methods. In addition, confirmed known mediators real dataset Finns plasma adiponectin level, which were missed by many believe will become useful tool generate hypotheses underlying facilitating functional follow-up.The R package is publicly available from CRAN at https://CRAN.R-project.org/package=SMUT.Supplementary data Bioinformatics online.