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.

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

Casalone E.;
2018-01-01

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.
2018
9
1
4674
4674
http://www.nature.com/ncomms/index.html
Cohort Studies; Gene Frequency; Genetic Variation; Humans; Alleles; Quantitative Trait, Heritable; Whole Genome Sequencing
Gilly A.; Suveges D.; Kuchenbaecker K.; Pollard M.; Southam L.; Hatzikotoulas K.; Farmaki A.-E.; Bjornland T.; Waples R.; Appel E.V.R.; Casalone E.; Melloni G.; Kilian B.; Rayner N.W.; Ntalla I.; Kundu K.; Walter K.; Danesh J.; Butterworth A.; Barroso I.; Tsafantakis E.; Dedoussis G.; Moltke I.; Zeggini E.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1729431
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