Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies...

Full description

Saved in:

Bibliographic Details
Published in:	PLoS genetics 2011-07, Vol.7 (7), p.e1002193-e1002193
Main Authors:	Lemaitre, Rozenn N, Tanaka, Toshiko, Tang, Weihong, Manichaikul, Ani, Foy, Millennia, Kabagambe, Edmond K, Nettleton, Jennifer A, King, Irena B, Weng, Lu-Chen, Bhattacharya, Sayanti, Bandinelli, Stefania, Bis, Joshua C, Rich, Stephen S, Jacobs, Jr, David R, Cherubini, Antonio, McKnight, Barbara, Liang, Shuang, Gu, Xiangjun, Rice, Kenneth, Laurie, Cathy C, Lumley, Thomas, Browning, Brian L, Psaty, Bruce M, Chen, Yii-Der I, Friedlander, Yechiel, Djousse, Luc, Wu, Jason H Y, Siscovick, David S, Uitterlinden, André G, Arnett, Donna K, Ferrucci, Luigi, Fornage, Myriam, Tsai, Michael Y, Mozaffarian, Dariush, Steffen, Lyn M
Format:	Article
Language:	eng
Subjects:	Aging Alleles Atherosclerosis Biology Continental Population Groups - genetics Diet Diseases Fatty acids Fatty Acids, Omega-3 - blood Female Genealogy Genetic aspects Genetic Loci - genetics Genome-Wide Association Study Genomes Grants Heart Hispanics Humans Kidney diseases Male Meta-analysis Metabolic Networks and Pathways - genetics Omega-3 fatty acids Phospholipids Physiological aspects Plasma Polymorphism, Single Nucleotide - genetics Studies United States
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.
ISSN:	1553-7404 1553-7390 1553-7404