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Discovery and fine-mapping of loci associated with monounsaturated fatty acids through trans-ethnic meta-analysis in Chinese and European populations.
Monday,2017-05-01 17:03 America/Los_Angeles — ecterry
| Title | Discovery and fine-mapping of loci associated with monounsaturated fatty acids through trans-ethnic meta-analysis in Chinese and European populations. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Hu, Y, Tanaka, T, Zhu, J, Guan, W, H Y Wu, J, Psaty, BM, McKnight, B, King, IB, Sun, Q, Richard, M, Manichaikul, A, Frazier-Wood, AC, Kabagambe, EK, Hopkins, PN, Ordovas, JM, Ferrucci, L, Bandinelli, S, Arnett, DK, Chen, Y-derI, Liang, S, Siscovick, DS, Tsai, MY, Rich, SS, Fornage, M, Hu, FB, Rimm, EB, Jensen, MK, Lemaitre, RN, Mozaffarian, D, Steffen, LM, Morris, AP, Li, H, Lin, X |
| Journal | J Lipid Res |
| Date Published | 2017 Mar 15 |
| ISSN | 1539-7262 |
| Abstract | <p>Monounsaturated fatty acids (MUFAs) are unsaturated fatty acids with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels were associated with cardiometabolic disorders including cardiovascular disease (CVD), type 2 diabetes (T2D) and metabolic syndrome (MS). Previous genome-wide association studies (GWAS) have identified seven loci for plasma and erythrocyte palmitoleic acid and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential causal variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in over 15,000 participants of Chinese- and European-ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor)>=8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor)>=61619;6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering ~95kb) to five (covering ~20kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were enriched in unsaturated fatty acids metabolism and signaling pathways. Our findings provided novel insight into the genetic basis relevant to MUFA metabolism and biology.</p> |
| DOI | 10.1194/jlr.P071860 |
| Alternate Journal | J. Lipid Res. |
| PubMed ID | 28298293 |
ePub date:
17/03