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

Marcia C. De Oliveira Otto, Rozenn N. Lemaitre, Qi Sun, Irena B. King, Jason H.Y. Wu, Ani Manichaikul, Stephen S. Rich, Michael Y. Tsai, Y. D. Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R. Irvin, Edmond K. Kabagambe, Donna K. Arnett, Majken K. Jensen, Barbara McKnight, Bruce M. Psaty, Lyn M. Steffen, Caren E. SmithUlf Risérus, Lars Lind, Frank B. Hu, Eric B. Rimm, David S. Siscovick, Dariush Mozaffarian

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Abstract

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.

Original languageEnglish (US)
Article numbere0196951
JournalPloS one
Volume13
Issue number5
DOIs
StatePublished - May 2018

Bibliographical note

Funding Information:
MO was supported by 3R01HL085710-07S1. CS was supported by K08 HL112845. QS was supported by the National Heart Lung and Blood Institute (R00-HL098459). DM was supported by National Heart Lung and Blood Institute R01HL085710, NIH/NHLBI R01HL115189, NIH/NHLBI R01HL130735, NIH/ NHLBI R01HL135920, Bill & Melinda Gates Foundation OPP1099505, FEMA EMW-2014-FP-00612. SA was supported by HL136700. Infrastructure for the Cohorts was supported in part by HL105756, HHSN268201300025C, HHSN268201300026C, U01-HG004729, U01-HL072524, CA186107 and N02-HL-64278. Complete funding information for all including studies are provided as supplemental material. The authors thank the staff and participants of the CHS study for their important contributions. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI. org. Acknowledgments: The authors thank the staff and participants of the ARIC, CARDIA, CHS, GOLDN, HPFS, MESA, NHS, and PIVUS studies for their important contributions.

Publisher Copyright:
© 2018 de Oliveira Otto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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