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

Wei Zhao; Asif Rasheed; Emmi Tikkanen; Jung-Jin Lee; Adam S Butterworth; Joanna M M Howson; Themistocles L Assimes; Rajiv Chowdhury; Marju Orho-Melander; Scott Damrauer; Aeron Small; Senay Asma; Minako Imamura; Toshimasa Yamauch; John C Chambers; Peng Chen; Bishwa R Sapkota; Nabi Shah; Sehrish Jabeen; Praveen Surendran; Yingchang Lu; Weihua Zhang; Atif Imran; Shahid Abbas; Faisal Majeed; Kevin Trindade; Nadeem Qamar; Nadeem Hayyat Mallick; Zia Yaqoob; Tahir Saghir; Syed Nadeem Hasan Rizvi; Anis Memon; Syed Zahed Rasheed; Fazal-Ur-Rehman Memon; Khalid Mehmood; Naveeduddin Ahmed; Irshad Hussain Qureshi; null Tanveer-Us-Salam; Wasim Iqbal; Uzma Malik; Narinder Mehra; Jane Z Kuo; Wayne H-H Sheu; Xiuqing Guo; Chao A Hsiung; Jyh-Ming J Juang; Børge G Nordestgaard; Anne Tybjaerg-Hansen; Marianne Benn; Ruth Frikke-Schmidt; CHD Exome+ Consortium

doi:10.1038/ng.3943

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

Wei Zhao, Asif Rasheed, Emmi Tikkanen, Jung-Jin Lee, Adam S Butterworth, Joanna M M Howson, Themistocles L Assimes, Rajiv Chowdhury, Marju Orho-Melander, Scott Damrauer, Aeron Small, Senay Asma, Minako Imamura, Toshimasa Yamauch, John C Chambers, Peng Chen, Bishwa R Sapkota, Nabi Shah, Sehrish Jabeen, Praveen SurendranYingchang Lu, Weihua Zhang, Atif Imran, Shahid Abbas, Faisal Majeed, Kevin Trindade, Nadeem Qamar, Nadeem Hayyat Mallick, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mehmood, Naveeduddin Ahmed, Irshad Hussain Qureshi, Tanveer-Us-Salam, Wasim Iqbal, Uzma Malik, Narinder Mehra, Jane Z Kuo, Wayne H-H Sheu, Xiuqing Guo, Chao A Hsiung, Jyh-Ming J Juang, Børge G Nordestgaard, Anne Tybjaerg-Hansen, Marianne Benn, Ruth Frikke-Schmidt, CHD Exome+ Consortium

Institut for Klinisk Medicin

91 Citationer (Scopus)

Abstract

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	49
Udgave nummer	10
Sider (fra-til)	1450-1457
Antal sider	8
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.3943
Status	Udgivet - 1 okt. 2017

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10.1038/ng.3943

http://europepmc.org/articles/pmc5844224?pdf=renderLicens: Andet

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Zhao, W., Rasheed, A., Tikkanen, E., Lee, J.-J., Butterworth, A. S., Howson, J. M. M., Assimes, T. L., Chowdhury, R., Orho-Melander, M., Damrauer, S., Small, A., Asma, S., Imamura, M., Yamauch, T., Chambers, J. C., Chen, P., Sapkota, B. R., Shah, N., Jabeen, S., ... CHD Exome+ Consortium (2017). Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease. Nature Genetics, 49(10), 1450-1457. https://doi.org/10.1038/ng.3943

Zhao, W, Rasheed, A, Tikkanen, E, Lee, J-J, Butterworth, AS, Howson, JMM, Assimes, TL, Chowdhury, R, Orho-Melander, M, Damrauer, S, Small, A, Asma, S, Imamura, M, Yamauch, T, Chambers, JC, Chen, P, Sapkota, BR, Shah, N, Jabeen, S, Surendran, P, Lu, Y, Zhang, W, Imran, A, Abbas, S, Majeed, F, Trindade, K, Qamar, N, Mallick, NH, Yaqoob, Z, Saghir, T, Rizvi, SNH, Memon, A, Rasheed, SZ, Memon, F-U-R, Mehmood, K, Ahmed, N, Qureshi, IH, Tanveer-Us-Salam, Iqbal, W, Malik, U, Mehra, N, Kuo, JZ, Sheu, WH-H, Guo, X, Hsiung, CA, Juang, J-MJ, Nordestgaard, BG , Tybjaerg-Hansen, A , Benn, M , Frikke-Schmidt, R & CHD Exome+ Consortium 2017, 'Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease', Nature Genetics, bind 49, nr. 10, s. 1450-1457. https://doi.org/10.1038/ng.3943

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abstract = "To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.",

keywords = "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, Comparative Study, Journal Article",

author = "Wei Zhao and Asif Rasheed and Emmi Tikkanen and Jung-Jin Lee and Butterworth, {Adam S} and Howson, {Joanna M M} and Assimes, {Themistocles L} and Rajiv Chowdhury and Marju Orho-Melander and Scott Damrauer and Aeron Small and Senay Asma and Minako Imamura and Toshimasa Yamauch and Chambers, {John C} and Peng Chen and Sapkota, {Bishwa R} and Nabi Shah and Sehrish Jabeen and Praveen Surendran and Yingchang Lu and Weihua Zhang and Atif Imran and Shahid Abbas and Faisal Majeed and Kevin Trindade and Nadeem Qamar and Mallick, {Nadeem Hayyat} and Zia Yaqoob and Tahir Saghir and Rizvi, {Syed Nadeem Hasan} and Anis Memon and Rasheed, {Syed Zahed} and Fazal-Ur-Rehman Memon and Khalid Mehmood and Naveeduddin Ahmed and Qureshi, {Irshad Hussain} and Tanveer-Us-Salam and Wasim Iqbal and Uzma Malik and Narinder Mehra and Kuo, {Jane Z} and Sheu, {Wayne H-H} and Xiuqing Guo and Hsiung, {Chao A} and Juang, {Jyh-Ming J} and Nordestgaard, {B{\o}rge G} and Anne Tybjaerg-Hansen and Marianne Benn and Ruth Frikke-Schmidt and {CHD Exome+ Consortium}",

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T1 - Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

AU - Zhao, Wei

AU - Rasheed, Asif

AU - Tikkanen, Emmi

AU - Lee, Jung-Jin

AU - Butterworth, Adam S

AU - Howson, Joanna M M

AU - Assimes, Themistocles L

AU - Chowdhury, Rajiv

AU - Orho-Melander, Marju

AU - Damrauer, Scott

AU - Small, Aeron

AU - Asma, Senay

AU - Imamura, Minako

AU - Yamauch, Toshimasa

AU - Chambers, John C

AU - Chen, Peng

AU - Sapkota, Bishwa R

AU - Shah, Nabi

AU - Jabeen, Sehrish

AU - Surendran, Praveen

AU - Lu, Yingchang

AU - Zhang, Weihua

AU - Imran, Atif

AU - Abbas, Shahid

AU - Majeed, Faisal

AU - Trindade, Kevin

AU - Qamar, Nadeem

AU - Mallick, Nadeem Hayyat

AU - Yaqoob, Zia

AU - Saghir, Tahir

AU - Rizvi, Syed Nadeem Hasan

AU - Memon, Anis

AU - Rasheed, Syed Zahed

AU - Memon, Fazal-Ur-Rehman

AU - Mehmood, Khalid

AU - Ahmed, Naveeduddin

AU - Qureshi, Irshad Hussain

AU - Tanveer-Us-Salam, null

AU - Iqbal, Wasim

AU - Malik, Uzma

AU - Mehra, Narinder

AU - Kuo, Jane Z

AU - Sheu, Wayne H-H

AU - Guo, Xiuqing

AU - Hsiung, Chao A

AU - Juang, Jyh-Ming J

AU - Nordestgaard, Børge G

AU - Tybjaerg-Hansen, Anne

AU - Benn, Marianne

AU - Frikke-Schmidt, Ruth

AU - CHD Exome+ Consortium

PY - 2017/10/1

Y1 - 2017/10/1

N2 - To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

AB - To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

KW - Asia

KW - Asian Continental Ancestry Group

KW - Biomarkers

KW - Comorbidity

KW - Coronary Disease

KW - Diabetes Mellitus, Type 2

KW - Europe

KW - European Continental Ancestry Group

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - HLA-DRB5 Chains

KW - Humans

KW - Metabolic Networks and Pathways

KW - Metabolic Syndrome X

KW - Molecular Targeted Therapy

KW - Mutation, Missense

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Comparative Study

KW - Journal Article

U2 - 10.1038/ng.3943

DO - 10.1038/ng.3943

M3 - Journal article

C2 - 28869590

SN - 1061-4036

VL - 49

SP - 1450

EP - 1457

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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