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 Smith, Ulf Risérus, Lars Lind, Frank B Hu, Eric B Rimm, David S Siscovick, Dariush Mozaffarian

Journal: PloS one 2018;13(5):e0196951

PMID: 29738550

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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.

Address: Division of Epidemiology, Human Genetics and Environmental Sciences, the University of Texas Health Science Center, School of Public Health, Houston, TX, United States of America.; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States of America.; Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health and Channing Division of Network Medicine, and Harvard Medical School, Boston, MA, United States of America.; Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.; University of New Mexico, Albuquerque, NM, United States of America.; The George Institute for Global Health and the Faculty of Medicine, University of New South Wales, Sydney, Australia.; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States of America.; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, United States of America.; Key Laboratory of Nutrition and Metabolism, the University of Texas Health Science Center, School of Public Health, Houston, TX, United States of America.; Department of Biostatistics, University of Minnesota, Minneapolis, MN, United States of America.; College of Public Health, University of Kentucky, Lexington, KY, United States of America.; Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.; Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, United States of America.; Department of Biostatistics, University of Washington, Seattle, WA, United States of America.; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States of America.; Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States of America.; School of Public Health, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America.; Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA, United States of America.; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.; The New York Academy of Medicine, New York, NY, United States of America.; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States of America.

DOI: 10.1371/journal.pone.0196951

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MeSH Terms: Fatty Acids, Genome-Wide Association Study, Humans, Introns, Lactase, Myosins, Polymorphism, Single Nucleotide, RNA, Long Noncoding, Sphingomyelins, Sphingosine N-Acyltransferase, Tumor Suppressor Proteins