title: Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.
abstract: Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.
authors.affiliation: 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: 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: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: 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: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center for Public Health Genomics and Department of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: 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: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.affiliation: 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: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine and Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA, New York Academy of Medicine, New York, NY, USA and.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.affiliation: Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Center for Public Health Genomics and.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine and.
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D044466:Asian People / Q000235:genetics; D001499:Bayes Theorem; D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; C000716847:FADS1 protein, human