Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits

Nat Commun. 2018 Nov 7;9(1):4674. doi: 10.1038/s41467-018-07070-8.


The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10-8; APOC3 and triglyceride levels, P = 1.5 × 10-26), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10-8), indicating a role for this gene in lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Cohort Studies
  • Gene Frequency / genetics
  • Genetic Variation
  • Humans
  • Quantitative Trait, Heritable*
  • Whole Genome Sequencing*