Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

ABSTRACT: Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distingu

SUBMITTER: Marigorta UM 

PROVIDER: S-EPMC5745037 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature