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

Arthur Gilly, Daniel Suveges, Karoline Kuchenbaecker, Martin Pollard, Lorraine Southam, Konstantinos Hatzikotoulas, Aliki-Eleni Farmaki, Thea Bjornland, Ryan Waples, Emil V. R. Appel, Elisabetta Casalone, Giorgio Melloni, Britt Kilian, Nigel W. Rayner, Ioanna Ntalla, Kousik Kundu, Klaudia Walter, John Danesh, Adam Butterworth, Inês Barroso, Emmanouil Tsafantakis, George Dedoussis, Ida Moltke and Eleftheria Zeggini ()
Additional contact information
Arthur Gilly: Wellcome Sanger Institute
Daniel Suveges: Wellcome Sanger Institute
Karoline Kuchenbaecker: Wellcome Sanger Institute
Martin Pollard: Wellcome Sanger Institute
Lorraine Southam: Wellcome Sanger Institute
Konstantinos Hatzikotoulas: Wellcome Sanger Institute
Aliki-Eleni Farmaki: University of Leicester
Thea Bjornland: Norwegian Institute of Science and Technology
Ryan Waples: University of Copenhagen
Emil V. R. Appel: University of Copenhagen
Elisabetta Casalone: University of Torino
Giorgio Melloni: Harvard Medical School
Britt Kilian: Wellcome Sanger Institute
Nigel W. Rayner: Wellcome Sanger Institute
Ioanna Ntalla: Queen Mary University of London
Kousik Kundu: Wellcome Sanger Institute
Klaudia Walter: Wellcome Sanger Institute
John Danesh: Wellcome Sanger Institute
Adam Butterworth: University of Cambridge
Inês Barroso: Wellcome Sanger Institute
Emmanouil Tsafantakis: Anogia Medical Centre
George Dedoussis: Harokopio University of Athens
Ida Moltke: University of Copenhagen
Eleftheria Zeggini: Wellcome Sanger Institute

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07070-8

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DOI: 10.1038/s41467-018-07070-8

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