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Nat Commun. 2015 Dec 22;6:10206. doi: 10.1038/ncomms10206.

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

Tang CS1, Zhang H2, Cheung CY3, Xu M4, Ho JC3, Zhou W2,5, Cherny SS1,6,7, Zhang Y8, Holmen O9,10, Au KW3, Yu H4, Xu L11, Jia J8, Porsch RM1, Sun L4, Xu W4, Zheng H4, Wong LY3, Mu Y12, Dou J12, Fong CH3, Wang S13, Hong X3, Dong L14, Liao Y14, Wang J14, Lam LS6, Su X15, Yan H15, Yang ML2, Chen J2, Siu CW3,16, Xie G17, Woo YC3, Wu Y18, Tan KC3,16, Hveem K9, Cheung BM3,16,19, Zöllner S20, Xu A3,16,19,21, Eugene Chen Y2, Jiang CQ22, Zhang Y23, Lam TH11, Ganesh SK2,24, Huo Y8, Sham PC1,6,7, Lam KS3,16,19, Willer CJ2,5,24, Tse HF3,16,25, Gao W26.

Author information

1
Department of Psychiatry, the University of Hong Kong, Hong Kong, China.
2
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
3
Department of Medicine, the University of Hong Kong, Hong Kong, China.
4
Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
5
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
6
Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
7
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
8
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
9
Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, 7600 Levanger, Norway.
10
St Olav Hospital, Trondheim University Hospital, 7030 Trondheim, Norway.
11
School of Public Health, the University of Hong Kong, Hong Kong, China.
12
Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
13
Beijing Hypertension League Institute, Beijing 100039, China.
14
Peking University Shougang Hospital, Beijing, China.
15
Department of Cardiology, Wuhan Asia Heart Hospital, China.
16
Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
17
Peking University Clinical Research Institute, Beijing, China.
18
Peking University Clinical Research Institute, Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China.
19
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
20
Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA.
21
Department of Pharmacology &Pharmacy, The University of Hong Kong, Hong Kong, China.
22
Guangzhou No.12 Hospital, Guangzhou 510620, China.
23
Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.
24
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
25
Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong, Hong Kong, China.
26
Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing 100191, China.

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.

PMID:
26690388
PMCID:
PMC4703860
DOI:
10.1038/ncomms10206
[Indexed for MEDLINE]
Free PMC Article

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