Journal
PLOS GENETICS
Volume 7, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002193
Keywords
-
Categories
Funding
- National Heart, Lung, and Blood Institute (NHLBI)
- National Human Genome Research Institute [HSN268200625226C, U01-HG-004729, U01-HG-004446, U01-HG-004424]
- National Institutes of Health
- NIH Roadmap for Medical Research
- National Institute of Neurological Disorders and Stroke [HL075366, HL080295, HL087652, HL105756, HL085251]
- National Institute on Aging [AG-023269, AG-15928, AG-20098, AG-027058]
- National Center for Research Resources [M01RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- Italian Ministry of Health [ICS110.1/RF97.71]
- U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]
- National Institute on Aging, National Institutes of Health, Baltimore, Maryland
- MESA
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [5K01DK082729-02]
- [UL1RR025005]
- [R01HL071051]
- [R01HL071205]
- [R01HL071250]
- [R01HL071251]
- [R01HL071252]
- [R01HL071258]
- [R01HL071259]
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Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from a-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=3x10(-64)) and lower levels of eicosapentaenoic acid (EPA, p=5x10(-58)) and docosapentaenoic acid (DPA, p=4x10(-154)). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p=2x10(-12)) and DPA (p=1x10(-43)) and lower docosahexaenoic acid (DHA, p=1x10(-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=1x10(-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.
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