PT  - JOURNAL ARTICLE
AU  - Arthur Gilly
AU  - Daniel Suveges
AU  - Karoline Kuchenbaecker
AU  - Martin Pollard
AU  - Lorraine Southam
AU  - Konstantinos Hatzikotoulas
AU  - Aliki-Eleni Farmaki
AU  - Thea Bjornland
AU  - Ryan Waples
AU  - Emil V. R. Appel
AU  - Elisabetta Casalone
AU  - Giorgio Melloni
AU  - Britt Kilian
AU  - Nigel W. Rayner
AU  - Ioanna Ntalla
AU  - Kousik Kundu
AU  - Klaudia Walter
AU  - John Danesh
AU  - Adam Butterworth
AU  - Inês Barroso
AU  - Emmanouil Tsafantakis
AU  - George Dedoussis
AU  - Ida Moltke
AU  - Eleftheria Zeggini
TI  - Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits
AID  - 10.1101/283481
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 283481
4099  - http://biorxiv.org/content/early/2018/03/16/283481.short
4100  - http://biorxiv.org/content/early/2018/03/16/283481.full
AB  - The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1,457 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 overlapping with, and mostly independent of established common variant signals (ADIPOQ and adiponectin, P=4.2×10−8; APOC3 and triglyceride levels, P=1.58×10−26; GGT1 and gamma-glutamyltransferase, P=2.3×10−6; UGT1A9 and bilirubin, P=1.9×10−8), and identify replicating evidence for a burden associated with triglyceride levels in FAM189A (P=2.26×10−8), indicating a role for this gene in lipid metabolism.