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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.

Nature communications

Clara S Tang, He Zhang, Chloe Y Y Cheung, Ming Xu, Jenny C Y Ho, Wei Zhou, Stacey S Cherny, Yan Zhang, Oddgeir Holmen, Ka-Wing Au, Haiyi Yu, Lin Xu, Jia Jia, Robert M Porsch, Lijie Sun, Weixian Xu, Huiping Zheng, Lai-Yung Wong, Yiming Mu, Jingtao Dou, Carol H Y Fong, Shuyu Wang, Xueyu Hong, Liguang Dong, Yanhua Liao, Jiansong Wang, Levina S M Lam, Xi Su, Hua Yan, Min-Lee Yang, Jin Chen, Chung-Wah Siu, Gaoqiang Xie, Yu-Cho Woo, Yangfeng Wu, Kathryn C B Tan, Kristian Hveem, Bernard M Y Cheung, Sebastian Zöllner, Aimin Xu, Y Eugene Chen, Chao Qiang Jiang, Youyi Zhang, Tai-Hing Lam, Santhi K Ganesh, Yong Huo, Pak C Sham, Karen S L Lam, Cristen J Willer, Hung-Fat Tse, Wei Gao

Affiliations

  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.

PMID: 26690388 PMCID: PMC4703860 DOI: 10.1038/ncomms10206

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.

References

  1. J Biol Chem. 2002 May 17;277(20):17564-70 - PubMed
  2. Hepatology. 2015 Jan;61(1):108-18 - PubMed
  3. Am J Hum Genet. 2004 Apr;74(4):765-9 - PubMed
  4. J Am Coll Cardiol. 2004 Sep 1;44(5):e213-310 - PubMed
  5. Clin Chem. 1972 Jun;18(6):499-502 - PubMed
  6. Science. 1986 Apr 4;232(4746):34-47 - PubMed
  7. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2685-91 - PubMed
  8. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D428-32 - PubMed
  9. J Lipid Res. 2005 Nov;46(11):2477-87 - PubMed
  10. N Engl J Med. 2006 Mar 23;354(12):1264-72 - PubMed
  11. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12569-74 - PubMed
  12. Prog Lipid Res. 2008 May;47(3):204-20 - PubMed
  13. Am J Hum Genet. 2008 Sep;83(3):311-21 - PubMed
  14. Nat Genet. 2008 Dec;40(12):1461-5 - PubMed
  15. Science. 2008 Dec 12;322(5908):1702-5 - PubMed
  16. Nat Genet. 2010 Feb;42(2):105-16 - PubMed
  17. J Biol Chem. 2010 Feb 26;285(9):6706-15 - PubMed
  18. Nat Rev Genet. 2010 May;11(5):356-66 - PubMed
  19. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7892-7 - PubMed
  20. Am J Hum Genet. 2010 Jun 11;86(6):832-8 - PubMed
  21. Nature. 2010 Aug 5;466(7307):707-13 - PubMed
  22. Hepatology. 2010 Sep;52(3):904-12 - PubMed
  23. PLoS Genet. 2011 Mar;7(3):e1001324 - PubMed
  24. Hepatology. 2011 Jun;53(6):1883-94 - PubMed
  25. Am J Hum Genet. 2011 Jul 15;89(1):82-93 - PubMed
  26. Diabetes Care. 2011 Sep;34(9):2113-5 - PubMed
  27. Nucleic Acids Res. 2012 Apr;40(7):e53 - PubMed
  28. Hum Genet. 2012 May;131(5):747-56 - PubMed
  29. Nat Genet. 2012 Jun;44(6):659-69 - PubMed
  30. PLoS One. 2012;7(6):e39362 - PubMed
  31. Nat Genet. 2012 Sep;44(9):991-1005 - PubMed
  32. Nature. 2012 Sep 6;489(7414):57-74 - PubMed
  33. Nature. 2012 Nov 1;491(7422):56-65 - PubMed
  34. J Hepatol. 2012 Dec;57(6):1276-82 - PubMed
  35. Nat Genet. 2013 Jan;45(1):25-33 - PubMed
  36. PLoS Genet. 2013 Mar;9(3):e1003379 - PubMed
  37. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):330-44 - PubMed
  38. PLoS One. 2013;8(7):e68095 - PubMed
  39. Nat Rev Genet. 2013 Oct;14(10):692-702 - PubMed
  40. Nat Genet. 2013 Nov;45(11):1345-52 - PubMed
  41. Nat Genet. 2013 Nov;45(11):1274-83 - PubMed
  42. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):645-55 - PubMed
  43. Nat Commun. 2013;4:2872 - PubMed
  44. Nat Genet. 2014 Feb;46(2):200-4 - PubMed
  45. Am J Hum Genet. 2014 Feb 6;94(2):223-32 - PubMed
  46. Am J Hum Genet. 2014 Feb 6;94(2):233-45 - PubMed
  47. Nat Genet. 2014 Apr;46(4):352-6 - PubMed
  48. Nat Genet. 2014 Apr;46(4):345-51 - PubMed
  49. Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):622-8 - PubMed
  50. Nat Rev Cardiol. 2014 May;11(5):276-89 - PubMed
  51. N Engl J Med. 2014 Jul 3;371(1):22-31 - PubMed
  52. N Engl J Med. 2014 Jul 3;371(1):32-41 - PubMed
  53. Nat Protoc. 2014 Nov;9(11):2643-62 - PubMed
  54. J Clin Endocrinol Metab. 2014 Nov;99(11):E2169-77 - PubMed
  55. Genomics. 2003 Jun;81(6):596-608 - PubMed

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