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 Journal Articles uri icon

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abstract

  • 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 <5�10 −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.

authors

  • Chasman, Daniel I
  • Pare, Guillaume
  • Zee, Robert YL
  • Parker, Alex N
  • Cook, Nancy R
  • Buring, Julie E
  • Kwiatkowski, David J
  • Rose, Lynda M
  • Smith, Joshua D
  • Williams, Paul T
  • Rieder, Mark J
  • Rotter, Jerome I
  • Nickerson, Deborah A
  • Krauss, Ronald M
  • Miletich, Joseph P
  • Ridker, Paul M

publication date

  • October 2008

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