Common and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program

J Hum Genet. 2023 Aug;68(8):565-570. doi: 10.1038/s10038-023-01147-z. Epub 2023 Apr 18.


All of Us is 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 between TTN and AF, GIGYF1 and T2D, ADAMTS17, ACAN, NPR2 and height, APOB, LDLR, PCSK9 and LDL. Our results are consistent with previous literature, indicating that the All of Us program is a reliable resource for advancing the understanding of complex diseases in diverse human populations.

MeSH terms

  • Carrier Proteins / genetics
  • Coronary Artery Disease* / epidemiology
  • Coronary Artery Disease* / genetics
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Population Health*
  • Proprotein Convertase 9 / genetics


  • PCSK9 protein, human
  • Proprotein Convertase 9
  • GIGYF1 protein, human
  • Carrier Proteins