title: Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.
abstract: Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Hong Kong, China.
authors.forename: Clara S
authors.identifier: http://orcid.org/0000-0003-0265-2638
authors.initials: CS
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Chloe Y Y
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Jenny C Y
authors.initials: JC
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Hong Kong, China.|Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Stacey S
authors.identifier: http://orcid.org/0000-0002-0269-3352
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, 7600 Levanger, Norway.|St Olav Hospital, Trondheim University Hospital, 7030 Trondheim, Norway.
authors.forename: Oddgeir
authors.initials: O
authors.lastname: Holmen
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Au
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
authors.forename: Haiyi
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Public Health, the University of Hong Kong, Hong Kong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Hong Kong, China.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Porsch
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Lai-Yung
authors.initials: LY
authors.lastname: Wong
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Dou
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Carol H Y
authors.initials: CH
authors.lastname: Fong
authors.affiliation: Beijing Hypertension League Institute, Beijing 100039, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Hong
authors.affiliation: Peking University Shougang Hospital, Beijing, China.
authors.forename: Liguang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Peking University Shougang Hospital, Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Peking University Shougang Hospital, Beijing, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Levina S M
authors.initials: LS
authors.lastname: Lam
authors.affiliation: Department of Cardiology, Wuhan Asia Heart Hospital, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Cardiology, Wuhan Asia Heart Hospital, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Min-Lee
authors.initials: ML
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: Peking University Clinical Research Institute, Beijing, China.
authors.forename: Gaoqiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Yu-Cho
authors.initials: YC
authors.lastname: Woo
authors.affiliation: Peking University Clinical Research Institute, Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China.
authors.forename: Yangfeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Kathryn C B
authors.initials: KC
authors.lastname: Tan
authors.affiliation: Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, 7600 Levanger, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors.forename: Bernard M Y
authors.initials: BM
authors.lastname: Cheung
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zöllner
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Pharmacology &Pharmacy, The University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Eugene Chen
authors.affiliation: Guangzhou No.12 Hospital, Guangzhou 510620, China.
authors.forename: Chao Qiang
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Public Health, the University of Hong Kong, Hong Kong, China.
authors.forename: Tai-Hing
authors.initials: TH
authors.lastname: Lam
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Santhi K
authors.initials: SK
authors.lastname: Ganesh
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Psychiatry, the University of Hong Kong, Hong Kong, China.|Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Cristen J
authors.identifier: http://orcid.org/0000-0001-5645-4966
authors.initials: CJ
authors.lastname: Willer
authors.affiliation: Department of Medicine, the University of Hong Kong, Hong Kong, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.|Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D044466:Asian People / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D059472:Exome / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides