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Article Dans Une Revue Nature Genetics Année : 2012

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Robert A. Scott (1) , Vasiliki Lagou (2, 3) , Ryan P. Welch (4) , Eleanor Wheeler (5) , May E. Montasser (6) , Jian'An Luan (1) , Reedik Maegi (2, 7) , Rona J. Strawbridge (8, 9) , Emil Rehnberg (8) , Stefan Gustafsson (8) , Stavroula Kanoni (10) , Laura J. Rasmussen-Torvik (11) , Loïc Yengo (12, 13) , Cécile Lecoeur (12, 13) , Dmitry Shungin (14, 15) , Serena Sanna (16) , Carlo Sidore (4, 17, 18) , Paul C. D. Johnson (19) , J. Wouter Jukema (20, 21) , Toby Johnson (22) , Anubha Mahajan (2) , Niek Verweij (23) , Gudmar Thorleifsson (24) , Jouke-Jan Hottenga (25, 26) , Sonia Shah (27) , Albert V. Smith (28, 29) , Bengt Sennblad (8) , Christian Gieger (30) , Perttu Salo (31) , Markus Perola (7, 31, 32) , Nicholas J. Timpson (33) , David M. Evans (33) , Beate St Pourcain , Ying Wu (34) , Jeanette S. Andrews (35) , Jennie Hui (36, 37, 38) , Lawrence F. Bielak (4) , Wei Zhao (4) , Momoko Horikoshi (2, 3) , Pau Navarro (39) , Aaron Isaacs (40, 41) , Jeffrey R. O'Connell (6) , Kathleen Stirrups (10) , Veronique Vitart (39) , Caroline Hayward (39) , Tonu Esko (7) , Evelin Mihailov (7) , Ross M. Fraser (39) , Tove Fall (8) , Benjamin F. Voight (42, 43) , Soumya Raychaudhuri (44) , Han Chen (45) , Cecilia M. Lindgren (2) , Andrew P. Morris (2) , Nigel W. Rayner (2, 3) , Neil Robertson (2, 3) , Denis Rybin (45) , Ching-Ti Liu (45) , Jacques S. Beckmann (46, 47) , Sara M. Willems (41) , Peter S. Chines (48) , Anne U. Jackson (4) , Hyun Min Kang (4) , Heather M. Stringham (4) , Kijoung Song (49) , Toshiko Tanaka (50) , John F. Peden , Anuj Goel , Andrew A. Hicks , Ping An , Martina Mueller-Nurasyid , Anders Franco-Cereceda , Lasse Folkersen , Letizia Marullo , Hanneke Jansen , Albertine J. Oldehinkel , Marcel Bruinenberg , James S. Pankow , Kari E. North , Nita G. Forouhi , Ruth J. F. Loos , Sarah Edkins , Tibor V. Varga , Goeran Hallmans , Heikki Oksa , Mulas Antonella , Ramaiah Nagaraja , Stella Trompet , Ian Ford , Stephan J. L. Bakker , Augustine Kong , Meena Kumari , Bruna Gigante , Christian Herder , Patricia B. Munroe , Mark Caulfield , Jula Antti , Massimo Mangino , Kerrin Small , Serge Hercberg (51)
1 Addenbrooke's Hospital
2 Wellcome Trust Ctr Human Genet
3 University of Oxford
4 Michigan State University [East Lansing]
5 Wellcome Trust Sanger Inst
6 University of Maryland [College Park]
7 University of Tartu
8 Karolinska Institutet [Stockholm]
9 Karolinska University Hospital [Stockholm]
10 The Wellcome Trust Sanger Institute [Cambridge]
11 Northwestern University [Evanston]
12 Université Lille Nord de France (COMUE)
13 Institut Pasteur de Lille
14 Skane University Hospital [Lund]
15 Umeå University
16 CNR - National Research Council of Italy | Consiglio Nazionale delle Ricerche
17 Istituto di Virologia Vegetale
18 UNISS - Università degli Studi di Sassari = University of Sassari [Sassari]
19 University of Glasgow
20 Netherlands Heart Institute
21 Universiteit Leiden = Leiden University
22 QMUL - Queen Mary University of London
23 University of Groningen [Groningen]
24 deCODE genetics [Reykjavik]
25 VU - Vrije Universiteit Amsterdam [Amsterdam]
26 IGE3 Inst Genet & Genom Geneva -
27 UCL - University College of London [London]
28 Icelandic Heart Association
29 University of Iceland [Reykjavik]
30 German Research Center for Environmental Health - Helmholtz Center München (GmbH)
31 Natl Inst Hlth & Welf
32 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
33 University of Bristol [Bristol]
34 NC State - North Carolina State University [Raleigh]
35 Wake Forest School of Medicine
36 Sir Charles Gairdner Hospital
37 UWA - The University of Western Australia
38 PathW Lab Med WA
39 Edin. - University of Edinburgh
40 Centre for Medical Systems Biology
41 Erasmus University Rotterdam
42 BROAD INSTITUTE - Broad Institute of MIT and Harvard
43 University of Pennyslvania
44 Brigham and Women’s Hospital [Boston, MA]
45 BU - Boston University [Boston]
46 Dept Med Genet
47 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
48 NHGRI - National Human Genome Research Institute
49 GlaxoSmithKline
50 National Institute on Aging
51 UREN - Unité de Recherche en Epidémiologie Nutritionnelle
Beate St Pourcain
  • Fonction : Auteur
Ying Wu
Tonu Esko
  • Fonction : Auteur
Han Chen
Kijoung Song
  • Fonction : Auteur
John F. Peden
  • Fonction : Auteur
Anuj Goel
  • Fonction : Auteur
Andrew A. Hicks
  • Fonction : Auteur
Ping An
  • Fonction : Auteur
Martina Mueller-Nurasyid
  • Fonction : Auteur
Anders Franco-Cereceda
  • Fonction : Auteur
Lasse Folkersen
  • Fonction : Auteur
Letizia Marullo
  • Fonction : Auteur
Hanneke Jansen
  • Fonction : Auteur
Albertine J. Oldehinkel
  • Fonction : Auteur
Marcel Bruinenberg
  • Fonction : Auteur
James S. Pankow
  • Fonction : Auteur
Kari E. North
  • Fonction : Auteur
Nita G. Forouhi
Ruth J. F. Loos
  • Fonction : Auteur
Sarah Edkins
  • Fonction : Auteur
Tibor V. Varga
Goeran Hallmans
  • Fonction : Auteur
Heikki Oksa
  • Fonction : Auteur
Mulas Antonella
  • Fonction : Auteur
Ramaiah Nagaraja
  • Fonction : Auteur
Stella Trompet
  • Fonction : Auteur
Ian Ford
  • Fonction : Auteur
Stephan J. L. Bakker
  • Fonction : Auteur
Augustine Kong
  • Fonction : Auteur
Meena Kumari
  • Fonction : Auteur
Bruna Gigante
  • Fonction : Auteur
Christian Herder
  • Fonction : Auteur
Patricia B. Munroe
  • Fonction : Auteur
Mark Caulfield
  • Fonction : Auteur
Jula Antti
  • Fonction : Auteur
Massimo Mangino
  • Fonction : Auteur
Kerrin Small
  • Fonction : Auteur

Résumé

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Dates et versions

hal-02653025 , version 1 (29-05-2020)

Identifiants

Citer

Robert A. Scott, Vasiliki Lagou, Ryan P. Welch, Eleanor Wheeler, May E. Montasser, et al.. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics, 2012, 44 (9), pp.991 - +. ⟨10.1038/ng.2385⟩. ⟨hal-02653025⟩
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