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dc.contributor.authorLi, Huaixingen
dc.contributor.authorGan, Weien
dc.contributor.authorLu, Lingen
dc.contributor.authorDong, Xiaoen
dc.contributor.authorHan, Xueyaoen
dc.contributor.authorHu, Chengen
dc.contributor.authorYang, Zhenen
dc.contributor.authorSun, Liangen
dc.contributor.authorBao, Weien
dc.contributor.authorLi, Pengtaoen
dc.contributor.authorHe, Meianen
dc.contributor.authorSun, Liangdanen
dc.contributor.authorWang, Yiqinen
dc.contributor.authorZhu, Jingwenen
dc.contributor.authorNing, Qianqianen
dc.contributor.authorTang, Yongen
dc.contributor.authorZhang, Rongen
dc.contributor.authorWen, Jieen
dc.contributor.authorWang, Dien
dc.contributor.authorZhu, Xilinen
dc.contributor.authorGuo, Kunquanen
dc.contributor.authorZuo, Xianboen
dc.contributor.authorGuo, Xiaohuien
dc.contributor.authorYang, Handongen
dc.contributor.authorZhou, Xianghaien
dc.contributor.authorDIAGRAM Consortium,en
dc.contributor.authorAGEN-T2D Consortium,en
dc.contributor.authorZhang, Xuejunen
dc.contributor.authorQi, Luen
dc.contributor.authorLoos, Ruthen
dc.contributor.authorHu, Frank Ben
dc.contributor.authorWu, Tangchunen
dc.contributor.authorLiu, Yingen
dc.contributor.authorLiu, Liegangen
dc.contributor.authorYang, Zeen
dc.contributor.authorHu, Renmingen
dc.contributor.authorJia, Weipingen
dc.contributor.authorJi, Linongen
dc.contributor.authorLi, Yixueen
dc.contributor.authorLin, Xuen
dc.date.accessioned2018-02-22T13:39:36Z
dc.date.available2018-02-22T13:39:36Z
dc.date.issued2013-01en
dc.identifier.issn0012-1797
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/273429
dc.description.abstractSubstantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDIAGRAM Consortiumen
dc.subjectAGEN-T2D Consortiumen
dc.subjectHumansen
dc.subjectDiabetes Mellitus, Type 2en
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectBlood Glucoseen
dc.subjectGuanine Nucleotide Exchange Factorsen
dc.subjectDNA-Binding Proteinsen
dc.subjectLinkage Disequilibriumen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectQuantitative Trait Locien
dc.subjectChinaen
dc.subjectAdiposityen
dc.subjectG-Protein-Coupled Receptor Kinase 5en
dc.subjectGenome-Wide Association Studyen
dc.subjectGenetic Locien
dc.titleA genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.en
dc.typeArticle
prism.endingPage298
prism.issueIdentifier1en
prism.publicationDate2013en
prism.publicationNameDiabetesen
prism.startingPage291
prism.volume62en
dc.identifier.doi10.17863/CAM.20459
dcterms.dateAccepted2012-06-23en
rioxxterms.versionofrecord10.2337/db12-0454en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2013-01en
dc.contributor.orcidLoos, Ruth [0000-0002-8532-5087]
dc.identifier.eissn1939-327X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MC_U106188470)
pubs.funder-project-idNIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC) (HTA/08/116/300)
pubs.funder-project-idMRC (MC_UU_12015/4)


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International