Abstract
To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
Original language | English (US) |
---|---|
Pages (from-to) | 981-990 |
Number of pages | 10 |
Journal | Nature Genetics |
Volume | 44 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2012 |
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In: Nature Genetics, Vol. 44, No. 9, 09.2012, p. 981-990.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
AU - Morris, Andrew P.
AU - Voight, Benjamin F.
AU - Teslovich, Tanya M.
AU - Ferreira, Teresa
AU - Segrè, Ayellet V.
AU - Steinthorsdottir, Valgerdur
AU - Strawbridge, Rona J.
AU - Khan, Hassan
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AU - Langenberg, Claudia
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AU - Müller-Nurasyid, Martina
AU - Pechlivanis, Sonali
AU - Rayner, N. William
AU - Scott, Laura J.
AU - Wiltshire, Steven
AU - Yengo, Loic
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AU - Raychaudhuri, Soumya
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AU - Dimas, Antigone S.
AU - Loos, Ruth J F
AU - Vedantam, Sailaja
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AU - Kraft, Peter
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AU - Van Dam, Rob M.
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AU - Chines, Peter S.
AU - Fischer, Krista
AU - Fontanillas, Pierre
AU - Holmen, Oddgeir L.
AU - Hunt, Sarah E.
AU - Jackson, Anne U.
AU - Kong, Augustine
AU - Lawrence, Robert
AU - Meyer, Julia
AU - Perry, John R B
AU - Platou, Carl G P
AU - Potter, Simon
AU - Rehnberg, Emil
AU - Robertson, Neil
AU - Sivapalaratnam, Suthesh
AU - Stančáková, Alena
AU - Stirrups, Kathleen
AU - Thorleifsson, Gudmar
AU - Tikkanen, Emmi
AU - Wood, Andrew R.
AU - Almgren, Peter
AU - Atalay, Mustafa
AU - Benediktsson, Rafn
AU - Bonnycastle, Lori L.
AU - Burtt, Noël
AU - Carey, Jason
AU - Charpentier, Guillaume
AU - Crenshaw, Andrew T.
AU - Doney, Alex S F
AU - Dorkhan, Mozhgan
AU - Edkins, Sarah
AU - Emilsson, Valur
AU - Eury, Elodie
AU - Forsen, Tom
AU - Gertow, Karl
AU - Gigante, Bruna
AU - Grant, George B.
AU - Groves, Christopher J.
AU - Guiducci, Candace
AU - Herder, Christian
AU - Hreidarsson, Astradur B.
AU - Hui, Jennie
AU - James, Alan
AU - Jonsson, Anna
AU - Rathmann, Wolfgang
AU - Klopp, Norman
AU - Kravic, Jasmina
AU - Krjutškov, Kaarel
AU - Langford, Cordelia
AU - Leander, Karin
AU - Lindholm, Eero
AU - Lobbens, Stéphane
AU - MäNnistö, Satu
AU - Mirza, Ghazala
AU - MüHleisen, Thomas W.
AU - Musk, Bill
AU - Parkin, Melissa
AU - Rallidis, Loukianos
AU - Saramies, Jouko
AU - Sennblad, Bengt
AU - Shah, Sonia
AU - Sigursson, Gunnar
AU - Silveira, Angela
AU - Steinbach, Gerald
AU - Thorand, Barbara
AU - Trakalo, Joseph
AU - Veglia, Fabrizio
AU - Wennauer, Roman
AU - Winckler, Wendy
AU - Zabaneh, Delilah
AU - Campbell, Harry
AU - Van Duijn, Cornelia
AU - Uitterlinden, Andre G.
AU - Hofman, Albert
AU - Sijbrands, Eric
AU - Abecasis, Goncalo R.
AU - Owen, Katharine R.
AU - Zeggini, Eleftheria
AU - Trip, Mieke D.
AU - Forouhi, Nita G.
AU - Syvänen, Ann Christine
AU - Eriksson, Johan G.
AU - Peltonen, Leena
AU - Nöthen, Markus M.
AU - Balkau, Beverley
AU - Palmer, Colin N A
AU - Lyssenko, Valeriya
AU - Tuomi, Tiinamaija
AU - Isomaa, Bo
AU - Hunter, David J.
AU - Qi, Lu
AU - Shuldiner, Alan R.
AU - Roden, Michael
AU - Barroso, Ines
AU - Wilsgaard, Tom
AU - Beilby, John
AU - Hovingh, Kees
AU - Price, Jackie F.
AU - Wilson, James F.
AU - Rauramaa, Rainer
AU - Lakka, Timo A.
AU - Lind, Lars
AU - Dedoussis, George
AU - NjøLstad, Inger
AU - Pedersen, Nancy L.
AU - Khaw, Kay Tee
AU - Wareham, Nicholas J.
AU - Keinanen-Kiukaanniemi, Sirkka M.
AU - Saaristo, Timo E.
AU - Korpi-HyöVäLti, Eeva
AU - Saltevo, Juha
AU - Laakso, Markku
AU - Kuusisto, Johanna
AU - Metspalu, Andres
AU - Collins, Francis S.
AU - Mohlke, Karen L.
AU - Bergman, Richard N.
AU - Tuomilehto, Jaakko
AU - Boehm, Bernhard O.
AU - Gieger, Christian
AU - Hveem, Kristian
AU - Cauchi, Stephane
AU - Froguel, Philippe
AU - Baldassarre, Damiano
AU - Tremoli, Elena
AU - Humphries, Steve E.
AU - Saleheen, Danish
AU - Danesh, John
AU - Ingelsson, Erik
AU - Ripatti, Samuli
AU - Salomaa, Veikko
AU - Erbel, Raimund
AU - JöCkel, Karl Heinz
AU - Moebus, Susanne
AU - Peters, Annette
AU - Illig, Thomas
AU - Faire, Ulf De
AU - Hamsten, Anders
AU - Morris, Andrew D.
AU - Donnelly, Peter J.
AU - Frayling, Timothy M.
AU - Hattersley, Andrew T.
AU - Boerwinkle, Eric
AU - Melander, Olle
AU - Kathiresan, Sekar
AU - Nilsson, Peter M.
AU - Deloukas, Panos
AU - Thorsteinsdottir, Unnur
AU - Groop, Leif C.
AU - Stefansson, Kari
AU - Hu, Frank
AU - Pankow, James S.
AU - Dupuis, Josée
AU - Meigs, James B.
AU - Altshuler, David
AU - Boehnke, Michael
AU - McCarthy, Mark I.
PY - 2012/9
Y1 - 2012/9
N2 - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
AB - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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UR - http://www.scopus.com/inward/citedby.url?scp=84868337361&partnerID=8YFLogxK
U2 - 10.1038/ng.2383
DO - 10.1038/ng.2383
M3 - Article
C2 - 22885922
AN - SCOPUS:84868337361
SN - 1061-4036
VL - 44
SP - 981
EP - 990
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -