Letter abstract
Nature Genetics 39, 513 - 516 (2007)
Published online: 25 February 2007 | doi:10.1038/ng1984
Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL
Stefano Romeo1,7, Len A Pennacchio2,7, Yunxin Fu3, Eric Boerwinkle3, Anne Tybjaerg-Hansen4, Helen H Hobbs1,6 & Jonathan C Cohen1,5
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.
- Donald W. Reynolds Cardiovascular Clinical Research Center, the Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
- Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA, and US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.
- Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science Center, Houston, Texas 77030, USA.
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
- Center for Human Nutrition and the University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
- Howard Hughes Medical Center at the University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
- These authors contributed equally to this work.
Correspondence to: Helen H Hobbs1,6 e-mail: helen.hobbs@utsouthwestern.edu
Correspondence to: Jonathan C Cohen1,5 e-mail: jonathan.cohen@utsouthwestern.edu
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