PLoS ONE (Jan 2018)

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

DOI
https://doi.org/10.1371/journal.pone.0196951
Journal volume & issue
Vol. 13, no. 5
p. e0196951

Abstract

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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.