 Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE ConsortiumRozenn N Lemaitre, Toshiko Tanaka, Weihong Tang, Ani Manichaikul, Millennia Foy, Edmond K Kabagambe, Jennifer A Nettleton, Irena B King, Lu-Chen Weng, Sayanti Bhattacharya, Stefania Bandinelli, Joshua C Bis, Stephen S Rich, David R Jacobs, Antonio Cherubini, Barbara McKnight, Shuang Liang, Xiangjun Gu, Kenneth Rice, Cathy C Laurie, Thomas Lumley, Brian L Browning, Bruce M Psaty, Yii- Der I Chen, Yechiel Friedlander, Luc Djousse, Jason H Y Wu, David S Siscovick, André G Uitterlinden, Donna K Arnett, Luigi Ferrucci, Myriam Fornage, Michael Y Tsai, Dariush Mozaffarian and Lyn M Steffen PLOS Genetics, 2011, vol. 7, issue 7, 1-12 Abstract: 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 = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). 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. Author Summary: Circulating long-chain n-3 polyunsaturated fatty acids (PUFAs) derive from fatty fish or from the conversion of the plant n-3 PUFA by elongation and desaturation. We looked for common genetic markers throughout the genome that might influence plasma phospholipid levels of the four major n-3 PUFAs in five large studies and pooled the results. We found that levels of all four n-3 PUFAs were associated with genetic markers in known desaturation and elongation genes. We also found evidence that conversion of the plant n-3 PUFA to longer chain n-3 PUFAs is less effective in people with certain desaturation-gene markers, which could be important for people who do not eat fish. We also found a marker in a gene involved in glucose metabolism, called the glucokinase regulator, to be associated with one intermediate n-3 PUFA. Some of these findings were seen across multiple race/ethnicities. Overall, these results have implications for how genes and the environment interact to influence circulating levels of fatty acids. Date: 2011 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1002193 DOI: 10.1371/journal.pgen.1002193 Access Statistics for this article More articles in PLOS Genetics from Public Library of Science |
Is your work missing from RePEc? Here is how to contribute.
Questions or problems? Check the EconPapers FAQ or send mail to .
EconPapers is hosted by the
School of Business at Örebro University.