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 BarrosoEmmanouil Tsafantakis, George Dedoussis, Ida Moltke, Eleftheria Zeggini

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Article number4674
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2018
Externally publishedYes


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