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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #355110

Research Project: Genomics, Nutrition, and Health

Location: Jean Mayer Human Nutrition Research Center On Aging

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

Author
item DE OLIVEIRA OTTO, MARCIA - University Of Texas
item LEMAITRE, ROZENN - University Of Washington
item SUN, QI - Harvard University
item KING, IRENA - University Of New Mexico
item WU, JASON - The George Institute For Global Health
item MANICHAIKUL, ANI - University Of Virginia
item RICH, STEPHEN - University Of Virginia
item TSAI, MICHAEL - University Of Minnesota
item CHEN, YII-DER - Ucla Medical Center
item FORNAGE, MYRIAM - University Of Texas
item WEIHUA, GUAN - University Of Minnesota
item ASLIBEKYAN, STELLA - University Of Kentucky
item IRVIN, MARGUERITE - University Of Kentucky
item KABAGAMBE, EDMOND - Vanderbilt University
item ARNETT, DONNA - University Of Kentucky
item JENSEN, MAJKEN - Brigham & Women'S Hospital
item MCKNIGHT, BARBARA - University Of Washington
item PSATY, BRUCE - University Of Washington
item STEFFEN, LYN - University Of Minnesota
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item RISERUS, ULF - Uppsala University
item LIND, LARS - Uppsala University
item HU, FRANK - Harvard University
item RIMM, ERIC - Harvard University
item SISCOVICK, DAVID - New York Academy Of Medicine
item MOZAFFARIAN, DARIUSH - Tufts University

Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2018
Publication Date: 5/8/2018
Citation: De Oliveira Otto, M.C., Lemaitre, R.N., Sun, Q., King, I., Wu, J.H., Manichaikul, A., Rich, S., Tsai, M.Y., Chen, Y., Fornage, M., Weihua, G., Aslibekyan, S., Irvin, M.R., Kabagambe, E.K., Arnett, D.K., Jensen, M.K., McKnight, B., Psaty, B.M., Steffen, L.M., Smith, C.E., Riserus, U., Lind, L., Hu, F., Rimm, E., Siscovick, D.S., Mozaffarian, D. 2018. Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids results from the CHARGE Consortium. PLoS One. 13(5):e0196951. https://doi.org/10.1371/journal.pone.0196951.
DOI: https://doi.org/10.1371/journal.pone.0196951

Interpretive Summary: Fatty acids in the bloodstream (circulating fatty acids) can indicate health status in that some fatty acids are associated with protection against disease and some are linked to greater disease risk. The composition of circulating fatty acids is influenced by the diet and also by the metabolism of foods, which in turn is influenced by genetics. The current study investigated a specific type of fatty acids, called odd-numbered chain saturated fatty acids, to determine whether genetic mutations influenced levels of these fatty acids in the blood. Importantly, dairy products are one of the sources of odd-chain saturated fatty acids in the diet. Using standard statistical methods, study investigators reported that genetics did not play a major role in determining the levels of this type of fatty acids. The overall conclusion of the study is that for some types of fatty acids, genetics does not play a major role in determining circulating concentrations. To investigate further, the investigators looked more closely at a gene that is involved with the metabolism of dairy products and found that a few mutations in that gene were related to odd-numbered chain saturated fatty acids concentrations. These results imply that consumption of dairy products, or mutations in the genes that metabolize dairy products, determine the concentrations of odd-numbered chain saturated fatty acids.

Technical Abstract: 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 = 1.37x10^-8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07x10^-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 = 4x10^-2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5x10^-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.