Genetic Loci Associated With Plasma Concentration of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-Wide Analysis With Replication

被引：114

作者：

Chasman, Daniel I. ^{[1
,2
]}

Pare, Guillaume ^{[1
,2
]}

Zee, Robert Y. L. ^{[1
,2
]}

Parker, Alex N. ^{[4
]}

Cook, Nancy R. ^{[1
,2
]}

Buring, Julie E. ^{[1
]}

Kwiatkowski, David J. ^{[2
]}

Rose, Lynda M. ^{[1
]}

Smith, Joshua D. ^{[3
]}

Williams, Paul T. ^{[5
]}

Rieder, Mark J. ^{[3
]}

Rotter, Jerome I. ^{[6
]}

Nickerson, Deborah A. ^{[3
]}

Krauss, Ronald M. ^{[5
,7
]}

Miletich, Joseph P.

Ridker, Paul M. ^{[1
,2
]}

机构：

[1] Harvard Univ, Ctr Cardiovasc Dis Prevent, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA

[2] Harvard Univ, Donald W Reynolds Ctr Cardiovasc Res, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA

[3] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[4] Amgen Inc, Cambridge, MA USA

[5] Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA

[6] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[7] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2008年 / 1卷 / 01期

关键词：

lipoproteins; lipids; cardiovascular diseases; population genetics;

D O I：

10.1161/CIRCGENETICS.108.773168

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Genome-wide genetic association analysis represents an opportunity for a comprehensive survey of the genes governing lipid metabolism, potentially revealing new insights or even therapeutic strategies for cardiovascular disease and related metabolic disorders. Methods and Results-We have performed large-scale, genome-wide genetic analysis among 6382 white women with replication in 2 cohorts of 970 additional white men and women for associations between common single-nucleotide polymorphisms and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (Apo) A1, and ApoB. Genome-wide associations (P<5x10(-8)) were found at the PCSK9 gene, the APOB gene, the LPL gene, the APOA1-APOA5 locus, the LIPC gene, the CETP gene, the LDLR gene, and the APOE locus. In addition, genome-wide associations with triglycerides at the GCKR gene confirm and extend emerging links between glucose and lipid metabolism. Still other genome-wide associations at the 1p13.3 locus are consistent with emerging biological properties for a region of the genome, possibly related to the SORT1 gene. Below genome-wide significance, our study provides confirmatory evidence for associations at 5 novel loci with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides reported recently in separate genome-wide association studies. The total proportion of variance explained by common variation at the genome-wide candidate loci ranges from 4.3% for triglycerides to 12.6% for ApoB. Conclusion-Genome-wide associations at the GCKR gene and near the SORT1 gene, as well as confirmatory associations at 5 additional novel loci, suggest emerging biological pathways for lipid metabolism among white women. (Circ Cardiovasc Genet. 2008;1:21-30.)

引用

页码：21 / U115

页数：49

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