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

TitleGenome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2018
AuthorsOtto, MC de Olive, Lemaitre, RN, Sun, Q, King, IB, H Y Wu, J, Manichaikul, A, Rich, SS, Tsai, MY, Chen, YD, Fornage, M, Weihua, G, Aslibekyan, S, Irvin, MR, Kabagambe, EK, Arnett, DK, Jensen, MK, McKnight, B, Psaty, BM, Steffen, LM, Smith, CE, Riserus, U, Lind, L, Hu, FB, Rimm, EB, Siscovick, DS, Mozaffarian, D
JournalPLoS One
Date Published2018
KeywordsFatty Acids, Genome-Wide Association Study, Humans, Introns, Lactase, Myosins, Polymorphism, Single Nucleotide, Sphingomyelins, Sphingosine N-Acyltransferase, Tumor Suppressor Proteins
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>
Alternate JournalPLoS ONE
PubMed ID29738550
PubMed Central IDPMC5940220
Grant ListR01 HL085710 / HL / NHLBI NIH HHS / United States
R01HL085710 / NH / NIH HHS / United States
CA186107 / NH / NIH HHS / United States
3R01HL085710-07S1 / NH / NIH HHS / United States
HL105756 / NH / NIH HHS / United States
HL136700 / NH / NIH HHS / United States
R01HL135920 / NH / NIH HHS / United States
N02-HL-64278 / NH / NIH HHS / United States
U01-HG004729 / NH / NIH HHS / United States
U01-HL072524 / NH / NIH HHS / United States
K08 HL112845 / NH / NIH HHS / United States
R01HL115189 / NH / NIH HHS / United States
R00-HL098459 / NH / NIH HHS / United States
R01HL130735 / NH / NIH HHS / United States
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