Common and Rare Variants Associated with Cardiometabolic Traits across 98,622 Whole-Genome Sequences in theAll of UsResearch Program

AbstractAll of Usis a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program’s genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations betweenTTNand AF,GIGYF1and T2D,ADAMTS17, ACAN, NPR2and height,APOB, LDLR, PCSK9and LDL. Our results are consistent with previous literature, indicating that theAll of Usprogram is a reliable resource for advancing the understanding of complex diseases in diverse human populations.