1. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis
- Author
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Jose M. Ordovas, Alex Parker, L. Adrienne Cupples, Anders Hamsten, Paul M. Ridker, Daniel I. Chasman, Robert Clarke, Samia Mora, Sekar Kathiresan, Gina M. Peloso, Guillaume Paré, Samuli Ripatti, Anders Mälarstig, Joseph P. Miletich, and J C Hopewell
- Subjects
Cancer Research ,Very low-density lipoprotein ,Magnetic Resonance Spectroscopy ,Apolipoprotein B ,Genome-wide association study ,030204 cardiovascular system & hematology ,Lipoprotein particle ,chemistry.chemical_compound ,0302 clinical medicine ,Genetics (clinical) ,Genetics and Genomics/Genetics of Disease ,Genetics ,Genetics and Genomics/Medical Genetics ,0303 health sciences ,biology ,Middle Aged ,3. Good health ,Cholesterol ,lipids (amino acids, peptides, and proteins) ,Female ,Genetics and Genomics/Gene Discovery ,Research Article ,medicine.medical_specialty ,lcsh:QH426-470 ,Lipoproteins ,MYLIP ,Genetics and Genomics/Complex Traits ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Particle Size ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Triglycerides ,030304 developmental biology ,Triglyceride ,Models, Genetic ,Reproducibility of Results ,lcsh:Genetics ,Endocrinology ,chemistry ,Genetic Loci ,biology.protein ,Cardiovascular Disorders/Cardiovascular Diseases in Women ,Lipoprotein ,Genome-Wide Association Study - 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, Author Summary Genome-wide association studies (GWAS) of plasma lipoprotein fractions hold great promise for understanding lipid metabolism and its central role in cardiovascular disease and related disorders. Conventional assays for lipoprotein status determine total cholesterol content of low- or high-density lipoprotein particles (LDL-C or HDL-C, respectively) or total plasma triglyceride content (as an estimate of very-low density lipoprotein particle concentration [VLDL]). All three measures have been targets for recent GWAS. However, a more precise target for GWAS of lipoprotein metabolism would be the concentration of the individual lipoprotein particles according to class (LDL, HDL, VLDL) and size (small, medium, and large), all of which can be measured by NMR-based methods. In a population of 17,296 women of European ancestry from the Women's Genome Health Study, we have performed a GWAS for 22 lipoprotein measures derived from NMR-based and conventional assays. We find 43 genetic loci involved in lipoprotein metabolism, including 10 novel loci. The results offer a clearer picture of common genetic influences on lipoprotein metabolism than available previously, including genetic effects on the distribution of LDL, HDL, and VLDL particle size, as well as on IDL and VLDL particle concentration, neither of which can be assessed by conventional measures.
- Published
- 2016