title: Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations.
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 atFADS1/2andPKD2L1[log10(Bayes factor) ≥ 8.07] and for gondoic acid atFADS1/2andGCKR[log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions atFADS1/2andGCKRloci. The greatest improvement was observed atGCKR, 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 ofPKD2L1,FADS1/2,GCKR, andHIF1ANwith palmitoleic acid and ofFADS1/2andLPCAT3with 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.
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Division of Biostatistics University of Minnesota, Minneapolis, MN.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jason H Y
authors.initials: JHY
authors.lastname: Wu
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.|Group Health Research Institute, Group Health Cooperative, Seattle, WA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Barbara
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authors.lastname: McKnight
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM.
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MA.
authors.forename: Qi
authors.initials: Q
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authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Melissa
authors.initials: M
authors.lastname: Richard
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA.|Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: USDA Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.|Department of Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD.
authors.forename: Luigi
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authors.lastname: Ferrucci
authors.affiliation: Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA.
authors.forename: Yii-Der I
authors.initials: YI
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.|Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.|New York Academy of Medicine, New York, NY.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Myriam
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authors.lastname: Fornage
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Cambridge, MA.
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authors.initials: MK
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authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN.
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.affiliation: Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China xlin@sibs.ac.cn lihx@sibs.ac.cn.
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China xlin@sibs.ac.cn lihx@sibs.ac.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D000090943:Delta-5 Fatty Acid Desaturase; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D044465:White People / Q000235:genetics*
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005229:Fatty Acids, Monounsaturated; C000716847:FADS1 protein, human
keywords: fatty acid/biosynthesis; fatty acid/desaturases; fatty acid/metabolism; genetics; monounsaturated fatty acid