Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk.

ABSTRACT: Biological interpretation of genome-wide association study data frequently involves assessing whether SNPs linked to a biological process, for example, binding of a transcription factor, show unsigned enrichment for disease signal. However, signed annotations quantifying whether each SNP allele promotes or hinders the biological process can enable stronger statements about disease mechanism. We introduce a method, signed linkage disequilibrium profile regression, for detecting genome-wide directional effects of signed functional annotations on disease risk. We validate the method via simulations and application to molecular quantitative trait loci in blood, recovering known transcriptional regulators. We apply the method to expression quantitative trait loci in 48 Genotype-Tissue Expressio

SUBMITTER: Reshef YA 

PROVIDER: S-EPMC6202062 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature