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

Published version
Peer-reviewed

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Type

Article

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Authors

Gilly, Arthur 
Suveges, Daniel 
Kuchenbaecker, Karoline 

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

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/L003120/1)
Medical Research Council (G0800270)
British Heart Foundation (None)
Medical Research Council (G0800270/1)
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