Journal
NATURE GENETICS
Volume 46, Issue 4, Pages 345-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.2926
Keywords
-
Categories
Funding
- National Heart, Lung and Blood Institute [HL094535, HL109946, HL068878, HL117491, HL117626]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK062370]
- National Human Genome Research Institute [HG007022]
Ask authors/readers for more resources
Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 Chi 10(-8)). One variant in TM6SF2 (encoding p. Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available