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; McRae, Allan F.1,4; Visscher, Peter M.1,4; Zeng, Jian 1; Yang, Jian1,2,4
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
卷号	9 期号:1 页码:2941
DOI	10.1038/s41467-018-04951-w
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
发表日期	2018-07-27
URL	查看原文
Pubmed记录号	30054458
PMC记录号	PMC6063971
Scopus记录号	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
自科自定义期刊分类	T2(B)类
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; Yang, Jian
作者单位	1.Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia; 2.Wenzhou Med Univ, Sch Ophthalmol & Optometry, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China; 3.Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia; 4.Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
通讯作者单位	眼视光学院（生物医学工程学院）、附属眼视光医院
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.