TY - JOUR T1 - Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium. JF - PLoS One Y1 - 2018 A1 - de Oliveira Otto, Marcia C A1 - Lemaitre, Rozenn N A1 - Sun, Qi A1 - King, Irena B A1 - Wu, Jason H Y A1 - Manichaikul, Ani A1 - Rich, Stephen S A1 - Tsai, Michael Y A1 - Chen, Y D A1 - Fornage, Myriam A1 - Weihua, Guan A1 - Aslibekyan, Stella A1 - Irvin, Marguerite R A1 - Kabagambe, Edmond K A1 - Arnett, Donna K A1 - Jensen, Majken K A1 - McKnight, Barbara A1 - Psaty, Bruce M A1 - Steffen, Lyn M A1 - Smith, Caren E A1 - Riserus, Ulf A1 - Lind, Lars A1 - Hu, Frank B A1 - Rimm, Eric B A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Fatty Acids KW - Genome-Wide Association Study KW - Humans KW - Introns KW - Lactase KW - Myosins KW - Polymorphism, Single Nucleotide KW - Sphingomyelins KW - Sphingosine N-Acyltransferase KW - Tumor Suppressor Proteins AB -

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<5×10-2).

CONCLUSIONS: 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.

VL - 13 IS - 5 ER -