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dc.contributor.authorScott, Robert Aen
dc.contributor.authorScott, Laura Jen
dc.contributor.authorMägi, Reediken
dc.contributor.authorMarullo, Letiziaen
dc.contributor.authorGaulton, Kyle Jen
dc.contributor.authorKaakinen, Marikaen
dc.contributor.authorPervjakova, Nataliaen
dc.contributor.authorPers, Tune Hen
dc.contributor.authorJohnson, Andrew Den
dc.contributor.authorEicher, John Den
dc.contributor.authorJackson, Anne Uen
dc.contributor.authorFerreira, Teresaen
dc.contributor.authorLee, Yejien
dc.contributor.authorMa, Clementen
dc.contributor.authorSteinthorsdottir, Valgerduren
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorQi, Luen
dc.contributor.authorVan Zuydam, Natalie Ren
dc.contributor.authorMahajan, Anubhaen
dc.contributor.authorChen, Hanen
dc.contributor.authorAlmgren, Peteren
dc.contributor.authorVoight, Ben Fen
dc.contributor.authorGrallert, Haralden
dc.contributor.authorMüller-Nurasyid, Martinaen
dc.contributor.authorRied, Janina Sen
dc.contributor.authorRayner, Nigel Wen
dc.contributor.authorRobertson, Neilen
dc.contributor.authorKarssen, Lennart Cen
dc.contributor.authorvan Leeuwen, Elisabeth Men
dc.contributor.authorWillems, Sara Men
dc.contributor.authorFuchsberger, Christianen
dc.contributor.authorKwan, Phoenixen
dc.contributor.authorTeslovich, Tanya Men
dc.contributor.authorChanda, Pritamen
dc.contributor.authorLi, Manen
dc.contributor.authorLu, Yingchangen
dc.contributor.authorDina, Christianen
dc.contributor.authorThuillier, Dorotheeen
dc.contributor.authorYengo, Loicen
dc.contributor.authorJiang, Longdaen
dc.contributor.authorSparso, Thomasen
dc.contributor.authorKestler, Hans Aen
dc.contributor.authorChheda, Himanshuen
dc.contributor.authorEisele, Lewinen
dc.contributor.authorGustafsson, Stefanen
dc.contributor.authorFrånberg, Mattiasen
dc.contributor.authorStrawbridge, Rona Jen
dc.contributor.authorBenediktsson, Rafnen
dc.contributor.authorHreidarsson, Astradur Ben
dc.contributor.authorKong, Augustineen
dc.contributor.authorSigurðsson, Gunnaren
dc.contributor.authorKerrison, Nicola Den
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorLiang, Limingen
dc.contributor.authorMeitinger, Thomasen
dc.contributor.authorRoden, Michaelen
dc.contributor.authorThorand, Barbaraen
dc.contributor.authorEsko, Tõnuen
dc.contributor.authorMihailov, Evelinen
dc.contributor.authorFox, Carolineen
dc.contributor.authorLiu, Ching-Tien
dc.contributor.authorRybin, Denisen
dc.contributor.authorIsomaa, Boen
dc.contributor.authorLyssenko, Valeriyaen
dc.contributor.authorTuomi, Tiinamaijaen
dc.contributor.authorCouper, David Jen
dc.contributor.authorPankow, James Sen
dc.contributor.authorGrarup, Nielsen
dc.contributor.authorHave, Christian Ten
dc.contributor.authorJørgensen, Marit Een
dc.contributor.authorJørgensen, Torbenen
dc.contributor.authorLinneberg, Allanen
dc.contributor.authorCornelis, Marilyn Cen
dc.contributor.authorvan Dam, Rob Men
dc.contributor.authorHunter, David Jen
dc.contributor.authorKraft, Peteren
dc.contributor.authorSun, Qien
dc.contributor.authorEdkins, Sarahen
dc.contributor.authorOwen, Katharine Ren
dc.contributor.authorPerry, Johnen
dc.contributor.authorWood, Andrew Ren
dc.contributor.authorZeggini, Eleftheriaen
dc.contributor.authorTajes-Fernandes, Juanen
dc.contributor.authorAbecasis, Goncalo Ren
dc.contributor.authorBonnycastle, Lori Len
dc.contributor.authorChines, Peter Sen
dc.contributor.authorStringham, Heather Men
dc.contributor.authorKoistinen, Heikki Aen
dc.contributor.authorKinnunen, Leenaen
dc.contributor.authorSennblad, Bengten
dc.contributor.authorMühleisen, Thomas Wen
dc.contributor.authorNöthen, Markus Men
dc.contributor.authorPechlivanis, Sonalien
dc.contributor.authorBaldassarre, Damianoen
dc.contributor.authorGertow, Karlen
dc.contributor.authorHumphries, Steve Een
dc.contributor.authorTremoli, Elenaen
dc.contributor.authorKlopp, Normanen
dc.contributor.authorMeyer, Juliaen
dc.contributor.authorSteinbach, Geralden
dc.contributor.authorWennauer, Romanen
dc.contributor.authorEriksson, Johan Gen
dc.contributor.authorMӓnnistö, Satuen
dc.contributor.authorPeltonen, Leenaen
dc.contributor.authorTikkanen, Emmien
dc.contributor.authorCharpentier, Guillaumeen
dc.contributor.authorEury, Elodieen
dc.contributor.authorLobbens, Stéphaneen
dc.contributor.authorGigante, Brunaen
dc.contributor.authorLeander, Karinen
dc.contributor.authorMcLeod, Olgaen
dc.contributor.authorBottinger, Erwin Pen
dc.contributor.authorGottesman, Omrien
dc.contributor.authorRuderfer, Douglasen
dc.contributor.authorBlüher, Matthiasen
dc.contributor.authorKovacs, Peteren
dc.contributor.authorTonjes, Ankeen
dc.contributor.authorMaruthur, Nisa Men
dc.contributor.authorScapoli, Chiaraen
dc.contributor.authorErbel, Raimunden
dc.contributor.authorJöckel, Karl-Heinzen
dc.contributor.authorMoebus, Susanneen
dc.contributor.authorde Faire, Ulfen
dc.contributor.authorHamsten, Andersen
dc.contributor.authorStumvoll, Michaelen
dc.contributor.authorDeloukas, Panagiotisen
dc.contributor.authorDonnelly, Peter Jen
dc.contributor.authorFrayling, Timothy Men
dc.contributor.authorHattersley, Andrew Ten
dc.contributor.authorRipatti, Samulien
dc.contributor.authorSalomaa, Veikkoen
dc.contributor.authorPedersen, Nancy Len
dc.contributor.authorBoehm, Bernhard Oen
dc.contributor.authorBergman, Richard Nen
dc.contributor.authorCollins, Francis Sen
dc.contributor.authorMohlke, Karen Len
dc.contributor.authorTuomilehto, Jaakkoen
dc.contributor.authorHansen, Torbenen
dc.contributor.authorPedersen, Olufen
dc.contributor.authorBarroso, Inesen
dc.contributor.authorLannfelt, Larsen
dc.contributor.authorIngelsson, Eriken
dc.contributor.authorLind, Larsen
dc.contributor.authorLindgren, Cecilia Men
dc.contributor.authorCauchi, Stephaneen
dc.contributor.authorFroguel, Philippeen
dc.contributor.authorLoos, Ruth JFen
dc.contributor.authorBalkau, Beverleyen
dc.contributor.authorBoeing, Heineren
dc.contributor.authorFranks, Paul Wen
dc.contributor.authorBarricarte Gurrea, Aurelioen
dc.contributor.authorPalli, Domenicoen
dc.contributor.authorvan der Schouw, Yvonne Ten
dc.contributor.authorAltshuler, Daviden
dc.contributor.authorGroop, Leif Cen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorSijbrands, Ericen
dc.contributor.authorvan Duijn, Cornelia Men
dc.contributor.authorFlorez, Jose Cen
dc.contributor.authorMeigs, James Ben
dc.contributor.authorBoerwinkle, Ericen
dc.contributor.authorGieger, Christianen
dc.contributor.authorStrauch, Konstantinen
dc.contributor.authorMetspalu, Andresen
dc.contributor.authorMorris, Andrew Den
dc.contributor.authorPalmer, Colin NAen
dc.contributor.authorHu, Frank Ben
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorStefansson, Karien
dc.contributor.authorDupuis, Joséeen
dc.contributor.authorMorris, Andrew Pen
dc.contributor.authorBoehnke, Michaelen
dc.contributor.authorMcCarthy, Mark Ien
dc.contributor.authorProkopenko, Ingaen
dc.contributor.authorDIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium,en
dc.date.accessioned2017-11-24T15:50:57Z
dc.date.available2017-11-24T15:50:57Z
dc.date.issued2017-11-01en
dc.identifier.issn0012-1797
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/269682
dc.description.abstractTo characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
dc.description.sponsorshipPlease refer to the manuscript or visit the publisher's website for funding infomation.
dc.languageengen
dc.publisherAmerican Diabetes Association
dc.titleAn Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.en
dc.typeArticle
prism.endingPage2902
prism.issueIdentifier11en
prism.publicationDate2017en
prism.publicationNameDiabetesen
prism.startingPage2888
prism.volume66en
dc.identifier.doi10.17863/CAM.15888
dcterms.dateAccepted2017-05-21en
rioxxterms.versionofrecord10.2337/db16-1253en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-11-01en
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.contributor.orcidBarroso, Ines [0000-0001-5800-4520]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.identifier.eissn1939-327X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/L00002/1)
cam.issuedOnline2017-05-31en


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