Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease
Nature Genetics 49, 1517 (2017).
doi:10.1038/ng.3936
Authors: Urko M Marigorta, Lee A Denson, Jeffrey S Hyams, Kajari Mondal, Jarod Prince, Thomas D Walters, Anne Griffiths, Joshua D Noe, Wallace V Crandall, Joel R Rosh, David R Mack, Richard Kellermayer, Melvin B Heyman, Susan S Baker, Michael C Stephens, Robert N Baldassano, James F Markowitz, Mi-Ok Kim, Marla C Dubinsky, Judy Cho, Bruce J Aronow, Subra Kugathasan & Greg Gibson
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 distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus ...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Urko M Marigorta Lee A Denson Jeffrey S Hyams Kajari Mondal Jarod Prince Thomas D Walters Anne Griffiths Joshua D Noe Wallace V Crandall Joel R Rosh David R Mack Richard Kellermayer Melvin B Heyman Susan S Baker Michael C Stephens Robert N Baldassano Jame Tags: Letter Source Type: research
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