Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium

Marcia C de Oliveira Otto, Rozenn N Lemaitre, Qi Sun, Irena B King, Jason H Y Wu, Ani Manichaikul, Stephen S Rich, Michael Y Tsai, Y D Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R Irvin, Edmond K Kabagambe, Donna K Arnett, Majken K Jensen, Barbara McKnight, Bruce M Psaty, Lyn M Steffen, Caren E Smith, Ulf Risérus, Lars Lind, Frank B Hu, Eric B Rimm, David S Siscovick and Dariush Mozaffarian

PLOS ONE, 2018, vol. 13, issue 5, 1-12

Abstract: Background: 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. Objective: To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. Design: 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. Results: 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

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0196951

DOI: 10.1371/journal.pone.0196951

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