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

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
Andrew P Morris Benjamin F Voight Tanya M Teslovich Teresa Ferreira Ayellet V Segrè Valgerdur Steinthorsdottir Rona J Strawbridge Hassan Khan Harald Grallert Inga Prokopenko Hyun Min Kang Christian Dina Tonu Esko Ross M Fraser Stavroula Kanoni Ashish Kumar Vasiliki Lagou Claudia Langenberg Jian'an Luan Cecilia M Lindgren Martina Müller-Nurasyid Sonali Pechlivanis N William Rayner Laura J Scott Steven Wiltshire Loic Yengo Leena Kinnunen Elizabeth J Rossin Soumya Raychaudhuri Andrew D Johnson Antigone S Dimas Ruth J F Loos Sailaja Vedantam Han Chen Jose C Florez Caroline Fox Ching-Ti Liu Denis Rybin David J Couper Wen Hong L Kao Man Li Marilyn C Cornelis Peter Kraft Qi Sun Rob M van Dam Heather M Stringham Peter S Chines Krista Fischer Pierre Fontanillas Oddgeir L Holmen Sarah E Hunt Anne U Jackson Augustine Kong Robert Lawrence Julia Meyer John R B Perry Carl G P Platou Simon Potter Emil Rehnberg Neil Robertson Suthesh Sivapalaratnam Alena Stančáková Kathleen Stirrups Gudmar Thorleifsson Emmi Tikkanen Andrew R Wood Peter Almgren Mustafa Atalay Rafn Benediktsson Lori L Bonnycastle Noël Burtt Jason Carey Guillaume Charpentier Andrew T Crenshaw Alex S F Doney Mozhgan Dorkhan Sarah Edkins Valur Emilsson Elodie Eury Tom Forsen Karl Gertow Bruna Gigante George B Grant Christopher J Groves Candace Guiducci Christian Herder Astradur B Hreidarsson Jennie Hui Alan James Anna Jonsson Wolfgang Rathmann Norman Klopp Jasmina Kravic Kaarel Krjutškov Cordelia Langford Karin Leander Eero Lindholm Stéphane Lobbens Satu Männistö Ghazala Mirza Thomas W Mühleisen Bill Musk Melissa Parkin Loukianos Rallidis Jouko Saramies Bengt Sennblad Sonia Shah Gunnar Sigurðsson Angela Silveira Gerald Steinbach Barbara Thorand Joseph Trakalo Fabrizio Veglia Roman Wennauer Wendy Winckler Delilah Zabaneh Harry Campbell Cornelia van Duijn Andre G Uitterlinden Albert Hofman Eric Sijbrands Goncalo R Abecasis Katharine R Owen Eleftheria Zeggini Mieke D Trip Nita G Forouhi Ann-Christine Syvänen Johan G Eriksson Leena Peltonen Markus M Nöthen Beverley Balkau Colin N A Palmer Valeriya Lyssenko Tiinamaija Tuomi Bo Isomaa David J Hunter Lu Qi Alan R Shuldiner Michael Roden Ines Barroso Tom Wilsgaard John Beilby Kees Hovingh Jackie F Price James F Wilson Rainer Rauramaa Timo A Lakka Lars Lind George Dedoussis Inger Njølstad Nancy L Pedersen Kay-Tee Khaw Nicholas J Wareham Sirkka M Keinanen-Kiukaanniemi Timo E Saaristo Eeva Korpi-Hyövälti Juha Saltevo Markku Laakso Johanna Kuusisto Andres Metspalu Francis S Collins Karen L Mohlke Richard N Bergman Jaakko Tuomilehto Bernhard O Boehm Christian Gieger Kristian Hveem Stephane Cauchi Philippe Froguel Damiano Baldassarre Elena Tremoli Steve E Humphries Danish Saleheen John Danesh Erik Ingelsson Samuli Ripatti Veikko Salomaa Raimund Erbel Karl-Heinz Jöckel Susanne Moebus Annette Peters Thomas Illig Ulf de Faire Anders Hamsten Andrew D Morris Peter J Donnelly Timothy M Frayling Andrew T Hattersley Eric Boerwinkle Olle Melander Sekar Kathiresan Peter M Nilsson Panos Deloukas Unnur Thorsteinsdottir Leif C Groop Kari Stefansson Frank Hu James S Pankow Josée Dupuis James B Meigs David Altshuler Michael Boehnke Mark I McCarthy

Nat Genet 2012 Sep 12;44(9):981-90. Epub 2012 Aug 12.

Wellcome Trust Centre for Human Genetics, University of Oxford, UK.

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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http://dx.doi.org/10.1038/ng.2383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442244PMC
September 2012
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