Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-02-25

AUTHORS

Stefano Romeo, Len A Pennacchio, Yunxin Fu, Eric Boerwinkle, Anne Tybjaerg-Hansen, Helen H Hobbs, Jonathan C Cohen

ABSTRACT

Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in ∼3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history. More... »

PAGES

513-516

Journal

TITLE

Nature Genetics

ISSUE

4

VOLUME

39

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1984

DOI

http://dx.doi.org/10.1038/ng1984

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003455365

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17322881


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