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

ABSTRACT

BACKGROUND: Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C150 and C170) are found in meats and dairy products, sources and metabolism of C190 and C230 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 C150, C170, C190, and C230 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 C230 levels. RESULTS: We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C150 or C230. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C170 level (P = 1.37×10-8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C190 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 C170 level (adjusted P = 4×10-2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C230 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 C170 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C230 may reflect a role of genetic factors in the synthesis of sphingomyelin.