Integration of rare expression outlier-associated variants improves polygenic risk prediction.

ABSTRACT: Polygenic risk scores (PRSs) quantify the contribution of multiple genetic loci to an individual's likelihood of a complex trait or disease. However, existing PRSs estimate this likelihood with common genetic variants, excluding the impact of rare variants. Here, we report on a method to identify rare variants associated with outlier gene expression and integrate their impact into PRS predictions for body mass index (BMI), obesity, and bariatric surgery. Between the top and bottom 10%, we observed a 20.8% increase in risk for obesity (p = 3 × 10^-14), 62.3% increase in risk for severe obesity (p = 1 × 10^-6), and median 5.29 years earlier onset for bariatric surgery (p = 0.008), as a function of expression outlier-associated rare variant burden when controlling for comm

SUBMITTER: Smail C 

PROVIDER: S-EPMC9247823 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature