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

Alisa K. Manning; Marie-France Hivert; Robert A. Scott; Jonna L. Grimsby; Nabila Bouatia-Naji; Han Chen; Denis Rybin; Ching-Ti Liu; Lawrence F. Bielak; Inga Prokopenko; Najaf Amin; Daniel Barnes; Gemma Cadby; Jouke-Jan Hottenga; Erik Ingelsson; Anne U. Jackson; Toby Johnson; Stavroula Kanoni; Claes Ladenvall; Vasiliki Lagou; Jari Lahti; Cécile Lecoeur; Yongmei Liu; Maria Teresa Martinez-Larrad; May E. Montasser; Pau Navarro; John R. B. Perry; Laura J. Rasmussen-Torvik; Perttu Salo; Naveed Sattar; Dmitry Shungin; Rona J. Strawbridge; Toshiko Tanaka; Cornelia M. van Duijn; Ping An; Mariza de Andrade; Jeanette S. Andrews; Thor Aspelund; Mustafa Atalay; Yurii Aulchenko; Beverley Balkau; Stefania Bandinelli; Jacques S. Beckmann; John P. Beilby; Claire Bellis; Richard N. Bergman; John Blangero; Mladen Boban; Michael Boehnke; Eric Boerwinkle; Lori L. Bonnycastle; Dorret I. Boomsma; Ingrid B. Borecki; Yvonne Boettcher; Claude Bouchard; Eric Brunner; Danijela Budimir; Harry Campbell; Olga Carlson; Peter S. Chines; Robert Clarke; Francis S. Collins; Arturo Corbatón-Anchuelo; David Couper; Ulf de Faire; George V. Dedoussis; Panos Deloukas; Maria Dimitriou; Josephine M. Egan; Gudny Eiriksdottir; Michael R. Erdos; Johan G. Eriksson; Elodie Eury; Luigi Ferrucci; Ian Ford; Nita G. Forouhi; Caroline S. Fox; Maria Grazia Franzosi; Paul W. Franks; Timothy M. Frayling; Philippe Froguel; Pilar Galan; Eco de Geus; Bruna Gigante; Nicole L. Glazer; Anuj Goel; Leif Groop; Vilmundur Gudnason; Goeran Hallmans; Anders Hamsten; Ola Hansson; Tamara B. Harris; Caroline Hayward; Simon Heath; Serge Hercberg; Andrew A. Hicks; Aroon Hingorani; Albert Hofman; Jennie Hui; Joseph Hung; DIAGRAM Consortium

doi:10.1038/ng.2274

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

Journal article

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

Alisa K. Manning, Marie-France Hivert, Robert A. Scott, Jonna L. Grimsby, Nabila Bouatia-Naji, Han Chen, Denis Rybin, Ching-Ti Liu, Lawrence F. Bielak, Inga Prokopenko, …

Nature genetics, Vol.44(6), pp.659-671

01/06/2012

DOI: https://doi.org/10.1038/ng.2274

PMID: 22581228

Abstract

Life Sciences

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.

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Title: A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
Creators: Alisa K. Manning - Boston University
Marie-France Hivert - Massachusetts General Hospital
Robert A. Scott - Medical Research Council
Jonna L. Grimsby - Massachusetts General Hospital
Nabila Bouatia-Naji - Institut Pasteur de Lille
Han Chen - Boston University
Denis Rybin - Boston University
Ching-Ti Liu - Boston University
Lawrence F. Bielak - University of Michigan–Ann Arbor
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Najaf Amin - Erasmus MC
Daniel Barnes - MRC Epidemiology Unit
Gemma Cadby - Ontario Institute for Cancer Research
Jouke-Jan Hottenga - Vrije Universiteit Amsterdam
Erik Ingelsson - Karolinska Institutet
Anne U. Jackson - University of Michigan–Ann Arbor
Toby Johnson - Queen Mary University of London
Stavroula Kanoni - Wellcome Sanger Institute
Claes Ladenvall - Lund University
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Jari Lahti - University of Helsinki
Cécile Lecoeur - Institut Pasteur de Lille
Yongmei Liu - Wake Forest University
Maria Teresa Martinez-Larrad - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
May E. Montasser - University of Maryland, Baltimore
Pau Navarro - MRC Institute of Genetics and Molecular Medicine
John R. B. Perry - Wellcome Centre for Human Genetics
Laura J. Rasmussen-Torvik - Northwestern University
Perttu Salo - Finnish Institute for Health and Welfare
Naveed Sattar - University of Glasgow
Dmitry Shungin - Lund University
Rona J. Strawbridge - Karolinska Institutet
Toshiko Tanaka - National Institute on Aging
Cornelia M. van Duijn - Erasmus MC
Ping An - Washington University in St. Louis
Mariza de Andrade - Mayo Clinic in Florida
Jeanette S. Andrews - Wake Forest University
Thor Aspelund - Icelandic Heart Association
Mustafa Atalay - University of Eastern Finland
Yurii Aulchenko - Erasmus MC
Beverley Balkau - Centre de recherche en Epidémiologie et Santé des Populations
Stefania Bandinelli - Azienda Sanitaria di Firenze
Jacques S. Beckmann - University of Lausanne
John P. Beilby - Queen Elizabeth II Medical Centre
Claire Bellis - Texas Biomedical Research Institute
Richard N. Bergman - University of Southern California
John Blangero - Texas Biomedical Research Institute
Mladen Boban - University of Split
Michael Boehnke - University of Michigan–Ann Arbor
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Lori L. Bonnycastle - National Human Genome Research Institute
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Ingrid B. Borecki - Washington University in St. Louis
Yvonne Boettcher - Leipzig University
Claude Bouchard - Pennington Biomedical Research Center
Eric Brunner - University College London
Danijela Budimir - University of Split
Harry Campbell - University of Edinburgh
Olga Carlson - National Institute on Aging
Peter S. Chines - National Human Genome Research Institute
Robert Clarke - University of Oxford
Francis S. Collins - National Human Genome Research Institute
Arturo Corbatón-Anchuelo - San Carlos Clinical Hospital
David Couper - University of North Carolina at Chapel Hill
Ulf de Faire - Karolinska Institutet
George V. Dedoussis - Harokopio University of Athens
Panos Deloukas - Wellcome Sanger Institute
Maria Dimitriou - Harokopio University of Athens
Josephine M. Egan - National Institute on Aging
Gudny Eiriksdottir - Icelandic Heart Association
Michael R. Erdos - National Human Genome Research Institute
Johan G. Eriksson - University of Helsinki
Elodie Eury - Université Lille Nord de France
Luigi Ferrucci - National Institute on Aging
Ian Ford - University of Glasgow
Nita G. Forouhi - MRC Epidemiology Unit
Caroline S. Fox - National Heart Lung and Blood Institute
Maria Grazia Franzosi - Mario Negri Institute for Pharmacological Research
Paul W. Franks - Lund University
Timothy M. Frayling - University of Exeter
Philippe Froguel - Université Lille Nord de France
Pilar Galan - Université Paris Cité
Eco de Geus
Bruna Gigante - Karolinska Institutet
Nicole L. Glazer - Boston University
Anuj Goel - University of Oxford
Leif Groop - Lund University
Vilmundur Gudnason - University of Iceland
Goeran Hallmans
Anders Hamsten - Karolinska Institutet
Ola Hansson - Lund University
Tamara B. Harris - National Institute on Aging
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Simon Heath
Serge Hercberg - Université Paris Cité
Andrew A. Hicks - Eurac Research
Aroon Hingorani - University College London
Albert Hofman - Netherlands Consortium for Healthy Ageing
Jennie Hui - Pathwest Laboratory Medicine
Joseph Hung - Queen Elizabeth II Medical Centre
DIAGRAM Consortium
Publication Details: Nature genetics, Vol.44(6), pp.659-671
Publisher: Nature Publishing Group
Number of pages: 13
Date published: 01/06/2012
Identifiers: 99928773802346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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