03320nas a2200421   4500000000100000008004100001100001700042700001600059700002100075700001500096700001100111700002000122700002100142700001700163700002000180700001700200700001700217700001900234700001300253700001400266700001800280700002000298700002400318700001600342700001600358700001400374700001600388700001100404700001600415700002200431700002100453700001600474245013500490300001300625490000700638520223900645022001402884       2018                            d1 aH Y Wu Jason1 aPsaty Bruce1 aMcKnight Barbara1 aKing Irena1 aSun Qi1 aManichaikul Ani1 aKabagambe Edmond1 aArnett Donna1 aSiscovick David1 aTsai Michael1 aRich Stephen1 aFornage Myriam1 aHu Frank1 aRimm Eric1 aJensen Majken1 aLemaitre Rozenn1 aMozaffarian Dariush1 aSteffen Lyn1 aOtto Marcia1 aLind Lars1 aRiserus Ulf1 aChen Y1 aWeihua Guan1 aAslibekyan Stella1 aIrvin Marguerite1 aSmith Caren00aGenome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium.  ae01969510 v133 a<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>  a1932-6203