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. 2009 Nov;5(11):e1000730.
doi: 10.1371/journal.pgen.1000730. Epub 2009 Nov 20.

Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis

Daniel I Chasman  1 , Guillaume Paré, Samia Mora, Jemma C Hopewell, Gina Peloso, Robert Clarke, L Adrienne Cupples, Anders Hamsten, Sekar Kathiresan, Anders Mälarstig, José M Ordovas, Samuli Ripatti, Alex N Parker, Joseph P Miletich, Paul M Ridker
Affiliations

Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis

Daniel I Chasman et al. PLoS Genet. 2009 Nov.

Abstract

While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (P<5x10(-8)) in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3), GMPR/MYLIP (6p22.3), BTNL2 (6p21.32), KLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism-including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles-all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

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Conflict of interest statement

Alex Parker and Joseph Miletich are employees of Amgen.

Figures

Figure 1
Figure 1. Loci with distinct classes of SNP associations among lipoprotein fractions with genome-wide significance.
(A) APOB locus (2p24.1), (B) APOA1-A5 locus (11q23.3). Recombination rates are from .
Figure 2
Figure 2. Variance explained in adjusted lipoprotein measures by common variation at the candidate loci by SNPs retained in model selection procedures.
See also Figure S2 and Figure S3.
See this image and copyright information in PMC

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