@article{23471,
  author = {H Y Wu Jason and Psaty Bruce and McKnight Barbara and King Irena and Sun Qi and Manichaikul Ani and Kabagambe Edmond and Arnett Donna and Siscovick David and Tsai Michael and Rich Stephen and Fornage Myriam and Hu Frank and Rimm Eric and Jensen Majken and Lemaitre Rozenn and Mozaffarian Dariush and Steffen Lyn and Otto Marcia and Lind Lars and Riserus Ulf and Chen Y and Weihua Guan and Aslibekyan Stella and Irvin Marguerite and Smith Caren},
  title = {Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium.},
  abstract = {<p><b>BACKGROUND: </b>Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established.</p><p><b>OBJECTIVE: </b>To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA.</p><p><b>DESIGN: </b>We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels.</p><p><b>RESULTS: </b>We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10-8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10-9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10-2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10-2).</p><p><b>CONCLUSIONS: </b>Our findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin.</p>},
  year = {2018},
  journal = {PLoS One},
  volume = {13},
  pages = {e0196951},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0196951},
  language = {eng},
}