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Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

Morris AP | Voight BF | Teslovich TM | Ferreira T | Segrè AV | Steinthorsdottir V | Strawbridge RJ | Khan H | Grallert H | Mahajan A | Prokopenko I | Kang HM | Dina C | Esko T | Fraser RM | Kanoni S | Kumar A | Lagou V | Langenberg C | Luan J | Lindgren CM | Müller-Nurasyid M | Pechlivanis S | Rayner NW | Scott LJ | Wiltshire S | Yengo L | Kinnunen L | Rossin EJ | Raychaudhuri S | Johnson AD | Dimas AS | Loos RJ | Vedantam S | Chen H | Florez JC | Fox C | Liu CT | Rybin D | Couper DJ | Kao WH | Li M | Cornelis MC | Kraft P | Sun Q | van Dam RM | Stringham HM | Chines PS | Fischer K | Fontanillas P | Holmen OL | Hunt SE | Jackson AU | Kong A | Lawrence R | Meyer J | Perry JR | Platou CG | Potter S | Rehnberg E | Robertson N | Sivapalaratnam S | Stančáková A | Stirrups K | Thorleifsson G | Tikkanen E | Wood AR | Almgren P | Atalay M | Benediktsson R | Bonnycastle LL | Burtt N | Carey J | Charpentier G | Crenshaw AT | Doney AS | Dorkhan M | Edkins S | Emilsson V | Eury E | Forsen T | Gertow K | Gigante B | Grant GB | Groves CJ | Guiducci C | Herder C | Hreidarsson AB | Hui J | James A | Jonsson A | Rathmann W | Klopp N | Kravic J | Krjutškov K | Langford C | Leander K | Lindholm E | Lobbens S | Männistö S | Mirza G | Mühleisen TW | Musk B | Parkin M | Rallidis L | Saramies J | Sennblad B | Shah S | Sigurðsson G | Silveira A | Steinbach G | Thorand B | Trakalo J | Veglia F | Wennauer R | Winckler W | Zabaneh D | Campbell H | van Duijn C | Uitterlinden AG | Hofman A | Sijbrands E | Abecasis GR | Owen KR | Zeggini E | Trip MD | Forouhi NG | Syvänen AC | Eriksson JG | Peltonen L | Nöthen MM | Balkau B | Palmer CN | Lyssenko V | Tuomi T | Isomaa B | Hunter DJ | Qi L | Wellcome Trust Case Control Consortium | Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators | Genetic Investigation of ANthropometric Traits (GIANT) Consortium | Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium | South Asian Type 2 Diabetes (SAT2D) Consortium | Shuldiner AR | Roden M | Barroso I | Wilsgaard T | Beilby J | Hovingh K | Price JF | Wilson JF | Rauramaa R | Lakka TA | Lind L | Dedoussis G | Njølstad I | Pedersen NL | Khaw KT | Wareham NJ | Keinanen-Kiukaanniemi SM | Saaristo TE | Korpi-Hyövälti E | Saltevo J | Laakso M | Kuusisto J | Metspalu A | Collins FS | Mohlke KL | Bergman RN | Tuomilehto J | Boehm BO | Gieger C | Hveem K | Cauchi S | Froguel P | Baldassarre D | Tremoli E | Humphries SE | Saleheen D | Danesh J | Ingelsson E | Ripatti S | Salomaa V | Erbel R | Jöckel KH | Moebus S | Peters A | Illig T | de Faire U | Hamsten A | Morris AD | Donnelly PJ | Frayling TM | Hattersley AT | Boerwinkle E | Melander O | Kathiresan S | Nilsson PM | Deloukas P | Thorsteinsdottir U | Groop LC | Stefansson K | Hu F | Pankow JS | Dupuis J | Meigs JB | Altshuler D | Boehnke M | McCarthy MI | DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
Nature genetics | Nov 19, 2012

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.

Pubmed ID: 22885922 RIS Download

Mesh terms: Case-Control Studies | Diabetes Mellitus, Type 2 | Female | Genes | Genetic Predisposition to Disease | Genome-Wide Association Study | Humans | Linkage Disequilibrium | Male | Pakistan | Polymorphism, Single Nucleotide | Sex Factors

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK093757
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  • Agency: NHLBI NIH HHS, Id: HHSN268201100012C
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  • Agency: Chief Scientist Office, Id: CZB/4/710
  • Agency: NIDDK NIH HHS, Id: R01 DK073490
  • Agency: NHLBI NIH HHS, Id: HHSN268201100009I
  • Agency: Chief Scientist Office, Id: CZB/4/672
  • Agency: Medical Research Council, Id: G0000649
  • Agency: Wellcome Trust, Id: 098017
  • Agency: NIDDK NIH HHS, Id: R01 DK058845
  • Agency: British Heart Foundation, Id: RG/08/008/25291
  • Agency: NIDDK NIH HHS, Id: R56 DK062370
  • Agency: NHGRI NIH HHS, Id: N01HG65403
  • Agency: NIDDK NIH HHS, Id: DK058845
  • Agency: Medical Research Council, Id: MC_UP_A100_1003
  • Agency: NINDS NIH HHS, Id: 1R21NS064908
  • Agency: Wellcome Trust, Id: GR072960
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  • Agency: Medical Research Council, Id: G8802774
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  • Agency: Department of Health, Id: N01HC25195
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  • Agency: PHS HHS, Id: GR081682
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  • Agency: Cancer Research UK, Id: HHSN268201100005I
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  • Agency: British Heart Foundation, Id: 090532
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  • Agency: NIDDK NIH HHS, Id: U01 DK062370
  • Agency: Wellcome Trust, Id: DK062370
  • Agency: NIDDK NIH HHS, Id: HHSN268201100009C
  • Agency: NIDDK NIH HHS, Id: HHSN268201100011C
  • Agency: NHLBI NIH HHS, Id: GR083270
  • Agency: PHS HHS, Id: HHSN268201100005C
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  • Agency: NINDS NIH HHS, Id: R01 AG010175
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  • Agency: Medical Research Council, Id: RG/07/008/23674
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