Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations |
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| Affiliation: | 2. Translational Gerontology Branch, National Institute on Aging, Baltimore, MD;4. Division of Biostatistics University of Minnesota, Minneapolis, MN;1010. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN;3. George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia;6. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA;1111. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA;11. Channing Division of Network Medicine, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA;8. Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MA;12. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX;10. Center for Public Health Genomics, University of Virginia, Charlottesville, VA;112. Department of Internal Medicine, University of Utah, Salt Lake City, UT;84. Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA;1212. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA;123. Department of Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain;106. Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy;88. New York Academy of Medicine, New York, NY |
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| Abstract: | MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 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) ≥ 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 94.8 kb) to 5 (covering 19.6 kb, 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 the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology. |
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| Keywords: | genetics fatty acid/desaturases fatty acid/metabolism fatty acid/biosynthesis monounsaturated fatty acid |
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