Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

Nature Genetics

Volumn 49, Issue 10, 2017, Pages 1450-1457

  Zhao, Wei ^a   Rasheed, Asif ^b   Tikkanen, Emmi ^c   Lee, Jung Jin ^a   Butterworth, Adam S ^d   Howson, Joanna M M ^d   Assimes, Themistocles L ^e   Chowdhury, Rajiv ^d   Orho Melander, Marju ^f   Damrauer, Scott ^a   Small, Aeron ^a   Asma, Senay ^g   Imamura, Minako ^h,i,j   Yamauch, Toshimasa ^k   Chambers, John C ^l,m,n   Chen, Peng ^o   Sapkota, Bishwa R ^p   Shah, Nabi ^b,q   Jabeen, Sehrish ^b   Surendran, Praveen ^d   Lu, Yingchang ^r,s   Zhang, Weihua ^l,m   Imran, Atif ^b   Abbas, Shahid ^t   Majeed, Faisal ^b   Trindade, Kevin ^a   Qamar, Nadeem ^u   Mallick, Nadeem Hayyat ^v   Yaqoob, Zia ^u   Saghir, Tahir ^u   Hasan Rizvi, Syed Nadeem ^u   Memon, Anis ^u   Rasheed, Syed Zahed ^w   Memon, Fazal Ur Rehman ^x   Mehmood, Khalid ^y   Ahmed, Naveeduddin ^y   Hussain Qureshi, Irshad ^z   Tanveer Us Salam, ^aa   Iqbal, Wasim ^aa   Malik, Uzma ^z   Mehra, Narinder ^ab   Kuo, Jane Z ^ac,ad   Sheu, Wayne H H ^ae,af   Guo, Xiuqing ^ad   Hsiung, Chao A ^ag   Juang, Jyh Ming J ^ah   Taylor, Kent D ^ad   Hung, Yi Jen ^ai   Lee, Wen Jane ^ae   Quertermous, Thomas ^e   Lee, I Te ^ae,af   Hsu, Chih Cheng ^ag   Bottinger, Erwin P ^r   Ralhan, Sarju ^aj   Teo, Yik Ying ^o,ak,al,am   Wang, Tzung Dau ^ah   Alam, Dewan S ^an   Di Angelantonio, Emanuele ^d   Epstein, Steve ^ao   Nielsen, Sune F ^ap   Nordestgaard, Borge G ^aq,ar   Tybjaerg Hansen, Anne ^aq,as   Young, Robin ^d   Benn, Marianne ^at   Frikke Schmidt, Ruth ^as   Kamstrup, Pia R ^aq   Jukema, J Wouter ^at,au   Sattar, Naveed ^av   Smit, Roelof ^at   Chung, Ren Hua ^ag   Liang, Kae Woei ^ae   Anand, Sonia ^g   Sanghera, Dharambir K ^p,aw,ax   Ripatti, Samuli ^c,ay,az   Loos, Ruth J F ^r,s   Kooner, Jaspal S ^l,n   Tai, E Shyong ^ba   Rotter, Jerome I ^ad   Ida Chen, Yii Der ^ad   Frossard, Philippe ^b   Maeda, Shiro ^h,i,j   Kadowaki, Takashi ^k   Reilly, Muredach ^bb   Pare, Guillaume ^g   Melander, Olle ^f   Salomaa, Veikko ^ay   Rader, Daniel J ^a   Danesh, John ^d,az   Voight, Benjamin F ^a,bc   Saleheen, Danish ^a,b   more..

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b Center for Non Communicable Diseases   (Pakistan)

^c UNIVERSITY OF HELSINKI   (Finland)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f LUND UNIVERSITY   (Sweden)

^g MCMASTER UNIVERSITY   (Canada)

^h Institute of Physical and Chemical Research   (Japan)

ⁱ UNIVERSITY OF THE RYUKYUS   (Japan)

^j UNIVERSITY HOSPITAL OF THE RYUKYUS   (Japan)

^k UNIVERSITY OF TOKYO   (Japan)

^l IMPERIAL COLLEGE LONDON   (United Kingdom)

^m EALING HOSPITAL NHS TRUST   (United Kingdom)

ⁿ IMPERIAL COLLEGE HEALTHCARE NHS TRUST   (United Kingdom)

^o NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

^p UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^q COMSATS Institute of Information Technology ^*  (Pakistan)

^r MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^s VANDERBILT INGRAM CANCER CENTER   (United States)

^t FAISALABAD MEDICAL UNIVERSITY   (Pakistan)

^u NATIONAL INSTITUTE OF CARDIOVASCULAR DISEASES   (Pakistan)

^v PUNJAB INSTITUTE OF CARDIOLOGY   (Pakistan)

^w Karachi Institute of Heart Diseases   (Pakistan)

^x Red Crescent Institute of Cardiology   (Pakistan)

^y CIVIL HOSPITAL   (Pakistan)

^z KING EDWARD MEDICAL UNIVERSITY   (Pakistan)

^aa Ameeruddin Medical College PGMI Lahore General Hospital M Phil Stud   (Pakistan)

^ab ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

^ac CardioDx   (United States)

^ad HARBOR UCLA MEDICAL CENTER   (United States)

^ae TAICHUNG VETERANS GENERAL HOSPITAL   (Taiwan)

^af NATIONAL YANG MING UNIVERSITY   (Taiwan)

^ag NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

^ah NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^ai TRI SERVICE GENERAL HOSPITAL   (Taiwan)

^aj Hero DMC Heart Institute Ludhiana   (India)

^ak GENOME INSTITUTE OF SINGAPORE   (Singapore)

^al SINGAPORE EYE RESEARCH INSTITUTE   (Singapore)

^am NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^an INTERNATIONAL CENTRE FOR DIARRHOEAL DISEASE RESEARCH   (Bangladesh)

^ao WASHINGTON HOSPITAL CENTER   (United States)

^ap FREDERIKSBERG HOSPITAL   (Denmark)

^aq GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^ar UNIVERSITY OF COPENHAGEN   (Denmark)

^as Rigshospitalet   (Denmark)

^at LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^au INTERUNIVERSITY CARDIOLOGY INSTITUTE OF THE NETHERLANDS   (Netherlands)

^av UNIVERSITY OF GLASGOW   (United Kingdom)

^aw UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^ax Oklahoma Center for Neuroscience   (United States)

^ay NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^az WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^ba Dept Medicine Endocrinol Diabet   (Singapore)

^bb Och Spine at New York Presbyterian Hospitals   (United States)

^bc UNIVERSITY OF PENNSYLVANIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID BINDING PROTEIN 4; ICOSAPENTAENOIC ACID ETHYL ESTER; BIOLOGICAL MARKER; HLA DRB5 ANTIGEN;

ARTICLE; CCDC92 GENE; CONTROLLED STUDY; EAST ASIAN; EUROPEAN; GENE; GENE LOCUS; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HLA DRB5 GENE; HUMAN; ISCHEMIC HEART DISEASE; MAJOR CLINICAL STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; SOUTH ASIAN; ASIA; ASIAN CONTINENTAL ANCESTRY GROUP; CAUCASIAN; COMORBIDITY; COMPARATIVE STUDY; CORONARY DISEASE; DIABETES MELLITUS, TYPE 2; EUROPE; GENETIC PREDISPOSITION; GENETICS; METABOLIC SYNDROME X; METABOLISM; MISSENSE MUTATION; MOLECULARLY TARGETED THERAPY; RISK FACTOR;

ASIA; ASIAN CONTINENTAL ANCESTRY GROUP; BIOMARKERS; COMORBIDITY; CORONARY DISEASE; DIABETES MELLITUS, TYPE 2; EUROPE; EUROPEAN CONTINENTAL ANCESTRY GROUP; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HLA-DRB5 CHAINS; HUMANS; METABOLIC NETWORKS AND PATHWAYS; METABOLIC SYNDROME X; MOLECULAR TARGETED THERAPY; MUTATION, MISSENSE; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS;

EID: 85030173238     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3943     Document Type: Article

References (54)

1. Guariguata, L. et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract. 103, 137-149 (2014).
2. Xu, J., Murphy, S.L., Kochanek, K.D. & Bastian, B.A. Deaths: final data for 2013. Natl. Vital Stat. Rep. 64, 1-119 (2016).
3. Rao Kondapally Seshasai, S. et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 364, 829-841 (2011).
4. Scott, R.A. et al. A genomic approach to therapeutic target validation identifies A glucose-lowering GLP1R variant protective for coronary heart disease. Sci. Transl. Med. 8, 341ra76 (2016).
5. Morris, A.P. et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44, 981-990 (2012).
6. Nikpay, M. et al. A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat. Genet. 47, 1121-1130 (2015).
7. Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236-1241 (2015).
8. Jansen, H. et al. Genetic variants primarily associated with type 2 diabetes are related to coronary artery disease risk. Atherosclerosis 241, 419-426 (2015).
9. Mahajan, A. et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet. 46, 234-244 (2014).
10. GTEx Consortium. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648-660 (2015).
11. Grundberg, E. et al. Mapping cis-and trans-regulatory effects across multiple tissues in twins. Nat. Genet. 44, 1084-1089 (2012).
12. Huyghe, J.R. et al. Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat. Genet. 45, 197-201 (2013).
13. Saleheen, D. et al. The Pakistan Risk of Myocardial Infarction Study: A resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia. Eur. J. Epidemiol. 24, 329-338 (2009).
14. Smith, G.D. & Ebrahim, S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32, 1-22 (2003).
15. Ross, S. et al. Mendelian randomization analysis supports the causal role of dysglycaemia and diabetes in the risk of coronary artery disease. Eur. Heart J. 36, 1454-1462 (2015).
16. Ahmad, O.S. et al. A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease. Nat. Commun. 6, 7060 (2015).
17. Willer, C.J. et al. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 45, 1274-1283 (2013).
18. Shungin, D. et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 518, 187-196 (2015).
19. Raychaudhuri, S. et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).
20. Rossin, E.J. et al. Proteins encoded in genomic regions associated with immunemediated disease physically interact and suggest underlying biology. PLoS Genet. 7, e1001273 (2011).
21. Wang, J., Duncan, D., Shi, Z. & Zhang, B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 41, W77-W83 (2013).
22. de Pontual, L. et al. Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in humans. Nat. Genet. 43, 1026-1030 (2011).
23. Kuro-o, M. et al. Mutation of the mouse klotho gene leads to A syndrome resembling ageing. Nature 390, 45-51 (1997).
24. O'Connor, L. et al. Bim: A novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 17, 384-395 (1998).
25. Suzuki, M. et al. Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and β-klotho expression decrease with fasting in northern elephant seals. Gen. Comp. Endocrinol. 216, 86-89 (2015).
26. Grimbert, P. et al. Truncation of C-mip (Tc-mip), A new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization. J. Exp. Med. 198, 797-807 (2003).
27. Madsen, L.S. et al. A humanized model for multiple sclerosis using HLA-DR2 and A human T-cell receptor. Nat. Genet. 23, 343-347 (1999).
28. Barrett, J.C. et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41, 703-707 (2009).
29. Sattar, N. et al. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet 375, 735-742 (2010).
30. Swerdlow, D.I. et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 385, 351-361 (2015).
31. White, J. et al. Association of lipid fractions with risks for coronary artery disease and diabetes. JAMA Cardiol. 1, 692-699 (2016).
32. Fall, T. et al. Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes. Diabetes 64, 2676-2684 (2015).
33. Schmidt, A.F. et al. PCSK9 genetic variants and risk of type 2 diabetes: A mendelian randomisation study. Lancet Diabetes Endocrinol. 5, 97-105 (2017).
34. Law, V. et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 42, D1091-D1097 (2014).
35. Ballantyne, C.M. et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am. J. Cardiol. 110, 984-992 (2012).
36. Ballantyne, C.M. et al. Effects of icosapent ethyl on lipoprotein particle concentration and size in statin-treated patients with persistent high triglycerides (the ANCHOR Study). J. Clin. Lipidol. 9, 377-383 (2015).
37. Boord, J.B. et al. Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 22, 1686-1691 (2002).
38. Hotamisligil, G.S. et al. Uncoupling of obesity from insulin resistance through A targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274, 1377-1379 (1996).
39. Makowski, L. et al. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat. Med. 7, 699-705 (2001).
40. Furuhashi, M. et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447, 959-965 (2007).
41. Burak, M.F. et al. Development of A therapeutic monoclonal antibody that targets secreted fatty acid-binding protein aP2 to treat type 2 diabetes. Sci. Transl. Med. 7, 319ra205 (2015).
42. Scott, R.A. et al. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes http://dx.doi.org/10.2337/db16-1253 (2017).
43. Auton, A. et al. A global reference for human genetic variation. Nature 526, 68-74 (2015).
44. Howie, B.N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).
45. Willer, C.J., Li, Y. & Abecasis, G.R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190-2191 (2010).
46. Feng, S., Liu, D., Zhan, X., Wing, M.K. & Abecasis, G.R. RAREMETAL: fast and powerful meta-analysis for rare variants. Bioinformatics 30, 2828-2829 (2014).
47. Liu, D.J. et al. Meta-analysis of gene-level tests for rare variant association. Nat. Genet. 46, 200-204 (2014).
48. Dastani, Z. et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 8, e1002607 (2012).
49. Evans, D.M. & Davey Smith, G. Mendelian randomization: new applications in the coming age of hypothesis-free causality. Annu. Rev. Genomics Hum. Genet. 16, 327-350 (2015).
50. Welter, D. et al. The NHGRI GWAS Catalog, A curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001-D1006 (2014).
51. Purcell, S. et al. PLINK: A tool set for whole-genome association and populationbased linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007).
52. Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369-375 (2012).
53. Doria, A., Patti, M.E. & Kahn, C.R. The emerging genetic architecture of type 2 diabetes. Cell Metab. 8, 186-200 (2008).
54. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289-300 (1995).