Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease.

Nat Genet
Authors
Keywords
Abstract

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

Year of Publication
2017
Journal
Nat Genet
Volume
49
Issue
12
Pages
1722-1730
Date Published
2017 Dec
ISSN
1546-1718
DOI
10.1038/ng.3978
PubMed ID
29083407
PubMed Central ID
PMC5899829
Links
Grant list
R35 HL135824 / HL / NHLBI NIH HHS / United States
R01 DK104371 / DK / NIDDK NIH HHS / United States
R01 HL127564 / HL / NHLBI NIH HHS / United States
K01 HL125751 / HL / NHLBI NIH HHS / United States
R01 HL108427 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
D43 TW009077 / TW / FIC NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States