Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

doi:10.1038/s41467-018-04951-w

科研成果详情

题名	Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes
作者	Xue, Angli 1; Wu, Yang 1; Zhu, Zhihong 1; Zhang, Futao 1; Kemper, Kathryn E.1; Zheng, Zhili1,2; Yengo, Loic 1; Lloyd-Jones, Luke R.1; Sidorenko, Julia 1,3; Wu, Yeda 1; Agbessi, Mawussé 5; Ahsan, Habibul 6; Alves, Isabel 5; Andiappan, Anand 7; Awadalla, Philip 5; Battle, Alexis 8; Beutner, Frank 9; Bonder, Marc Jan 10; Boomsma, Dorret 11; Christiansen, Mark 12; Claringbould, Annique 10; Deelen, Patrick 10; Esko, Tõnu 13; Favé, Marie-Julie 5; Franke, Lude 10; Frayling, Timothy 14; Gharib, Sina 15; Gibson, Gregory 16; Hemani, Gibran 17; Jansen, Rick 11; Kähönen, Mika 18,19; Kalnapenkis, Anette 13; Kasela, Silva 13; Kettunen, Johannes 20; Kim, Yungil 8; Kirsten, Holger 21; Kovacs, Peter 22; Krohn, Knut 23; Kronberg-Guzman, Jaanika 13; Kukushkina, Viktorija 13; Kutalik, Zoltan 24; Lee, Bernett 7; Lehtimäki, Terho 25; Loeffler, Markus 21; Marigorta, Urko M.16; Metspalu, Andres 13; Milani, Lili 13; Müller-Nurasyid, Martina 26; Nauck, Matthias 27; Nivard, Michel 11; Penninx, Brenda 11; Perola, Markus 20; Pervjakova, Natalia 13; Pierce, Brandon 6; Powell, Joseph 1; Prokisch, Holger 28; Psaty, Bruce 29; Raitakari, Olli 30,31; Ring, Susan 32; Ripatti, Samuli 20; Rotzschke, Olaf 7; Ruëger, Sina 24; Saha, Ashis 8; Scholz, Markus 21; Schramm, Katharina 26; Seppälä, Ilkka 25; Stumvoll, Michael 22; Sullivan, Patrick 33; Teumer, Alexander 34; Thiery, Joachim 35; Tong, Lin 6; Tönjes, Anke 36; van Dongen, Jenny 11; van Meurs, Joyce 37; Verlouw, Joost 37; Völker, Uwe 38; Võsa, Urmo 10; Yaghootkar, Hanieh 14; Zeng, Biao 16; McRae, Allan F.1,4; Visscher, Peter M.1,4; Zeng, Jian 1; Yang, Jian1,2,4
发表日期	2018-07-27
发表期刊	NATURE COMMUNICATIONS 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	GENETIC ARCHITECTURE ; MISSING HERITABILITY ; SUSCEPTIBILITY LOCI ; RARE ; COMMON ; IDENTIFICATION ; GWAS ; METAANALYSIS ; DYSFUNCTION ; ACTIVATION
摘要	Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a metaanalysis of genome-wide association studies (GWAS) with similar to 16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.
资助项目	Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1107258, 1083656, 1078037, 1113400]; Australian Research CouncilAustralian Research Council [DP160101056, DP160103860, DP160102400]; US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 MH100141, P01 GM099568, R01 GM075091, R01 AG042568, R21 ES025052]; Sylvia & Charles Viertel Charitable Foundation; F.G. Meade Scholarship; University of QueenslandUniversity of Queensland; dbGaP [phs000674.v2.p2]; UK Biobank [12505]; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [R21ES025052] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM075091, P01GM099568] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF MENTAL HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH100141] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG042568] Funding Source: NIH RePORTER
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	2041-1723
EISSN	2041-1723
卷号	9 期号:1 页码:2941
DOI	10.1038/s41467-018-04951-w
页数	14
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000439969600003
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	30054458
PMC记录号	PMC6063971
SCOPUSEID	2-s2.0-85050718439
ESI高被引论文	2021-05 ; 2021-07 ; 2021-09 ; 2022-01 ; 2022-03 ; 2022-07 ; 2022-09 ; 2022-11 ; 2023-01 ; 2023-03 ; 2023-05 ; 2023-07 ; 2023-09 ; 2023-11 ; 2024-01 ; 2024-03 ; 2024-05 ; 2024-07 ; 2024-09
自科自定义期刊分类	T2(B)类
通讯作者地址	[Zeng, Jian]Institute for Molecular Bioscience,The University of Queensland,Brisbane,4072,Australia
Scopus学科分类	Chemistry (all);Biochemistry, Genetics and Molecular Biology (all);Physics and Astronomy (all)
TOP期刊	TOP期刊
引用统计	被引频次：293[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6996
专题	眼视光学院（生物医学工程学院）、附属眼视光医院
通讯作者	Zeng, Jian
作者单位	1.Institute for Molecular Bioscience,The University of Queensland,Brisbane,4072,Australia; 2.The Eye Hospital,School of Ophthalmology & Optometry,Wenzhou Medical University,Wenzhou,325027,China; 3.Estonian Genome Center,Institute of Genomics,University of Tartu,Tartu,51010,Estonia; 4.Queensland Brain Institute,The University of Queensland,Brisbane,4072,Australia; 5.Computational Biology,Ontario Institute for Cancer Research,Toronto,M5G 0A3,Canada; 6.Department of Public Health Sciences,University of Chicago,Chicago,60637,United States; 7.Singapore Immunology Network,Agency for Science,Technology and Research,Singapore,138648,Singapore; 8.Department of Computer Science,Johns Hopkins University,Baltimore,21218,United States; 9.Heart Center Leipzig,Universität Leipzig,Leipzig,04289,Germany; 10.Department of Genetics,University Medical Centre Groningen,Groningen,9713 GZ,Netherlands; 11.Faculty of Genes,Behavior and Health,Vrije Universiteit Amsterdam,Amsterdam,1081 HV,Netherlands; 12.Cardiovascular Health Research Unit,University of Washington,Seattle,98195,United States; 13.Estonian Genome Center,University of Tartu,Tartu,50090,Estonia; 14.Exeter Medical School,University of Exeter,Exeter,EX4 4QD,United Kingdom; 15.Department of Medicine,University of Washington,Seattle,98195,United States; 16.School of Biological Sciences,Georgia Tech,Atlanta,30332,United States; 17.MRC Integrative Epidemiology Unit,University of Bristol,Bristol,BS8 1TH,United Kingdom; 18.Department of Clinical Physiology,Tampere University Hospital,Tampere,33521,Finland; 19.Faculty of Medicine and Life Sciences,University of Tampere,Tampere,33100,Finland; 20.National Institute for Health and Welfare,University of Helsinki,Helsinki,00100,Finland; 21.Institut für Medizinische InformatiK,Statistik und Epidemiologie,LIFE – Leipzig Research Center for Civilization Diseases,Universität Leipzig,Leipzig,04103,Germany; 22.IFB Adiposity Diseases,Department of Medicine,Universität Leipzig,Leipzig,04103,Germany; 23.Interdisciplinary Center for Clinical Research,Faculty of Medicine,Universität Leipzig,Leipzig,04103,Germany; 24.Lausanne University Hospital,Lausanne,1011,Switzerland; 25.Department of Clinical Chemistry,Fimlab Laboratories and Faculty of Medicine and Life Sciences,University of Tampere,Tampere,33110,Finland; 26.Institute of Genetic Epidemiology,Helmholtz Zentrum München,München,81377,Germany; 27.Institute of Clinical Chemistry and Laboratory Medicine,University Medicine Greifswald,Greifswald,17489,Germany; 28.Institute of Human Genetics,Helmholtz Zentrum München,München,81675,Germany; 29.Cardiovascular Health Research Unit,Departments of Epidemiology,Medicine,and Health Services,University of Washington,Seattle,98195,United States; 30.Department of Clinical Physiology and Nuclear Medicine,Turku University Hospital,Turku,20521,Finland; 31.University of Turku,Turku,20500,Finland; 32.School of Social and Community Medicine,University of Bristol,Bristol,BS8 1TH,United Kingdom; 33.Department of Medical Epidemiology and Biostatistics,Karolinska Institute,Solna,171 77,Sweden; 34.Institute for Community Medicine,University Medicine Greifswald,Greifswald,17489,Germany; 35.Institute for Laboratory Medicine,LIFE – Leipzig Research Center for Civilization Diseases,Universität Leipzig,Leipzig,04107,Germany; 36.Division of Endocrinology and Nephrology,Department of Medicine,Universität Leipzig,Leipzig,04103,Germany; 37.Department of Internal Medicine,Erasmus Medical Centre,Rotterdam,3015 CE,Netherlands; 38.Interfaculty Institute for Genetics and Functional Genomics,University Medicine Greifswald,Greifswald,17489,Germany
推荐引用方式 GB/T 7714	Xue, Angli,Wu, Yang,Zhu, Zhihong,et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes[J]. NATURE COMMUNICATIONS,2018,9(1):2941.
APA	Xue, Angli., Wu, Yang., Zhu, Zhihong., Zhang, Futao., Kemper, Kathryn E.., ... & Yang, Jian. (2018). Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. NATURE COMMUNICATIONS, 9(1), 2941.
MLA	Xue, Angli,et al."Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes".NATURE COMMUNICATIONS 9.1(2018):2941.