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Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium
Open accessAbstract
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.
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Metadata
- Authors
- Lemaitre, R. N., Tanaka, T., Tang, W., Manichaikul, A., Foy, M., Kabagambe, E. K., Nettleton, J. A., King, I. B., Weng, L.-C., Bhattacharya, S., Bandinelli, S., Bis, J. C., Rich, S. S., Jacobs, D. R., Cherubini, A., McKnight, B., Liang, S., Gu, X., Rice, K., Laurie, C. C., Lumley, T., Browning, B. L., Psaty, B. M., Chen, Y.-D. I., Friedlander, Y., Djousse, L., Wu, J. H. Y., Siscovick, D. S., Uitterlinden, A. G., Arnett, D. K., Ferrucci, L., Fornage, M., Tsai, M. Y., Mozaffarian, D., & Steffen, L. M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-07-28
- Volume
- 7
- Issue
- 7
- Pages
- e1002193
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W2097695579
- Cited by
- 411
- References
- 49
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lemaitre, R. N., Tanaka, T., Tang, W., Manichaikul, A., Foy, M., Kabagambe, E. K., Nettleton, J. A., King, I. B., Weng, L.-C., Bhattacharya, S., Bandinelli, S., Bis, J. C., Rich, S. S., Jacobs, D. R., Cherubini, A., McKnight, B., Liang, S., Gu, X., Rice, K., . . . Steffen, L. M. (2011). Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1002193
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