Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Gilly, Arthur
Suveges, Daniel
Kuchenbaecker, Karoline
Pollard, Martin https://orcid.org/0000-0001-8738-0920
Southam, Lorraine https://orcid.org/0000-0002-7546-9650
Abstract
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.
Description
Keywords
Alleles, Cohort Studies, Gene Frequency, Genetic Variation, Humans, Quantitative Trait, Heritable, Whole Genome Sequencing
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
2041-1723
Volume Title
9
Publisher
Springer Science and Business Media LLC
Publisher DOI
Sponsorship
Medical Research Council (MR/L003120/1)
Medical Research Council (G0800270)
British Heart Foundation (None)
Medical Research Council (G0800270/1)
Medical Research Council (G0800270)
British Heart Foundation (None)
Medical Research Council (G0800270/1)