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Article Dans Une Revue Nature Genetics Année : 2012

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Alisa K. Manning (1, 2, 3, 4) , Marie-France Hivert (5, 6) , Robert A. Scott (7) , Jonna L. Grimsby (5, 8) , Nabila Bouatia-Naji (9, 10) , Han Chen (1) , Denis Rybin (1) , Ching-Ti Liu (1) , Lawrence F. Bielak (11) , Inga Prokopenko (12, 13) , Najaf Amin (14) , Daniel Barnes (7) , Gemma Cadby (15, 16) , Jouke-Jan Hottenga (17) , Erik Ingelsson (18) , Anne U. Jackson (19) , Toby Johnson (20) , Stavroula Kanoni (21) , Claes Ladenvall (22, 23) , Vasiliki Lagou (12, 13) , Jari Lahti (24) , Cécile Lecoeur (9, 10) , Yongmei Liu (25) , Maria Teresa Martinez-Larrad (26) , May E. Montasser (27) , Pau Navarro (28) , John R. B. Perry (13, 29, 30) , Laura J. Rasmussen-Torvik (31) , Perttu Salo (32) , Naveed Sattar (33) , Dmitry Shungin (22, 22, 34) , Rona J. Strawbridge (35) , Toshiko Tanaka (36) , Cornelia M. van Duijn (14, 37, 38) , Ping An (39) , Mariza de Andrade (40) , Jeanette S. Andrews (41) , Thor Aspelund (42, 43) , Mustafa Atalay (44) , Yurii Aulchenko (14) , Beverley Balkau (45, 46) , Stefania Bandinelli (47) , Jacques S. Beckmann (48, 49) , John P. Beilby (50) , Claire Bellis (51) , Richard N. Bergman (52) , John Blangero (51) , Mladen Boban (53) , Michael Boehnke (19) , Eric Boerwinkle (54) , Lori L. Bonnycastle (36) , Dorret I. Boomsma (17) , Ingrid B. Borecki (39) , Yvonne Boettcher (55) , Claude Bouchard (56) , Eric Brunner (57) , Danijela Budimir (53) , Harry Campbell (28) , Olga Carlson (36) , Peter S. Chines (36) , Robert Clarke (58) , Francis S. Collins (36) , Arturo Corbatón-Anchuelo (59) , David Couper (60) , Ulf de Faire (35) , George V. Dedoussis (61) , Panos Deloukas (21) , Maria Dimitriou (61) , Josephine M. Egan (62) , Gudny Eiriksdottir (42) , Michael R. Erdos (36) , Johan G. Eriksson (24, 63, 64, 32) , Elodie Eury (9, 10) , Luigi Ferrucci (62) , Ian Ford , Nita G. Forouhi , Caroline S. Fox , Maria Grazia Franzosi , Paul W. Franks , Timothy M. Frayling , Philippe Froguel (9, 10) , Pilar Galan , Eco de Geus , Bruna Gigante (35) , Nicole L. Glazer , Anuj Goel , Leif Groop , Vilmundur Gudnason (43) , Goeran Hallmans , Anders Hamsten , Ola Hansson , Tamara B. Harris , Caroline Hayward (28) , Simon Heath , Serge Hercberg (65) , Andrew A. Hicks , Aroon Hingorani , Albert Hofman (14, 38) , Jennie Hui , Joseph Hung
1 BU - Boston University [Boston]
2 Broad Institute of Harvard and MIT
3 Massachusetts General Hospital
4 Department of Genetics [Boston]
5 Massachusetts General Hospital [Boston]
6 Department of Medicine
7 Addenbrooke's Hospital
8 Department of Medicine
9 Institut Pasteur de Lille
10 Université Lille Nord de France (COMUE)
11 Department of Epidemiology
12 OCDEM - Oxford Centre for Diabetes, Endocrinology and Metabolism
13 The Wellcome Trust Centre for Human Genetics [Oxford]
14 Department of Epidemiology
15 Ontario Institute for Cancer Research
16 MSH - Mount Sinai Hospital [Toronto, Canada]
17 VU - Vrije Universiteit Amsterdam [Amsterdam]
18 MEB - Department of Medical Epidemiology and Biostatistics
19 University of Michigan [Ann Arbor]
20 QMUL - Queen Mary University of London
21 The Wellcome Trust Sanger Institute [Cambridge]
22 Skane University Hospital [Lund]
23 Diabetes Centre
24 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
25 Wake Forest School of Medicine
26 Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
27 University of Maryland School of Medicine
28 Edin. - University of Edinburgh
29 University of Exeter
30 King‘s College London
31 Northwestern University [Evanston]
32 National Institute of Health and Welfare
33 Institute of Cardiovascular and Medical Sciences
34 Umeå University
35 Karolinska Institutet [Stockholm]
36 NIH - National Institutes of Health [Bethesda, MD, USA]
37 Centre for Medical Systems Biology
38 Netherlands Genomics Initiative
39 WUSTL - Washington University in Saint Louis
40 Department of Health Sciences Research
41 Wake Forest University
42 Icelandic Heart Association
43 University of Iceland [Reykjavik]
44 Institute of Biomedicine, Physiology
45 INSERM - Institut National de la Santé et de la Recherche Médicale
46 CESP - Centre de recherche en épidémiologie et santé des populations
47 Azienda Sanitaria Firenze
48 Department of Medical Genetics
49 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
50 Queen Elizabeth II Medical Centre
51 Research Institute
52 USC - University of Southern California
53 University of Split
54 UTHealth - The University of Texas Health Science Center at Houston
55 Leipzig University / Universität Leipzig
56 Pennington Biomedical Research Center
57 Department of Epidemiology & Public Health
58 University of Oxford
59 San Carlos Clinical Hospital
60 University of North Carolina
61 Harokopio University
62 National Institute on Aging
63 Folkhälsan Research Centre
64 Vaasa Central Hospital
65 UREN - Unité de Recherche en Epidémiologie Nutritionnelle
Han Chen
Daniel Barnes
Claire Bellis
John Blangero
  • Fonction : Auteur
Mladen Boban
  • Fonction : Auteur
Ian Ford
  • Fonction : Auteur
Nita G. Forouhi
Caroline S. Fox
  • Fonction : Auteur
Maria Grazia Franzosi
  • Fonction : Auteur
Paul W. Franks
  • Fonction : Auteur
Timothy M. Frayling
  • Fonction : Auteur
Pilar Galan
  • Fonction : Auteur
Eco de Geus
  • Fonction : Auteur
Nicole L. Glazer
  • Fonction : Auteur
Anuj Goel
  • Fonction : Auteur
Leif Groop
  • Fonction : Auteur
Goeran Hallmans
  • Fonction : Auteur
Anders Hamsten
  • Fonction : Auteur
Ola Hansson
  • Fonction : Auteur
Tamara B. Harris
  • Fonction : Auteur
Simon Heath
  • Fonction : Auteur
Andrew A. Hicks
  • Fonction : Auteur
Aroon Hingorani
  • Fonction : Auteur
Jennie Hui
  • Fonction : Auteur
Joseph Hung
  • Fonction : Auteur

Résumé

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Dates et versions

hal-02650726 , version 1 (29-05-2020)

Identifiants

Citer

Alisa K. Manning, Marie-France Hivert, Robert A. Scott, Jonna L. Grimsby, Nabila Bouatia-Naji, et al.. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nature Genetics, 2012, 44 (6), pp.659-671. ⟨10.1038/ng.2274⟩. ⟨hal-02650726⟩
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