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

Peer reviewed

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

PMCID: PMC3613127

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 - without role: Alisa K. Manning - Boston University
Marie-France Hivert - Massachusetts General Hospital
Robert A. Scott - Addenbrooke's Hospital
Jonna L. Grimsby - Massachusetts General Hospital
Nabila Bouatia-Naji - Institut Pasteur
Han Chen - Boston University
Denis Rybin - Boston University
Ching-Ti Liu - Boston University
Lawrence F. Bielak - Department of Epidemiology
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Najaf Amin - Department of Epidemiology
Daniel Barnes - Addenbrooke's Hospital
Gemma Cadby - Ontario Institute for Cancer Research
Jouke-Jan Hottenga - Vrije Universiteit Amsterdam
Erik Ingelsson - Department of Medical Epidemiology and Biostatistics
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
Yongmei Liu - Wake Forest School of Medicine
Maria Teresa Martinez-Larrad - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
May E. Montasser - University of Maryland School of Medicine
Pau Navarro - University of Edinburgh
John R. B. Perry - Wellcome Centre for Human Genetics
Laura J. Rasmussen-Torvik - Northwestern University [Evanston]
Perttu Salo - National Institute of Health and Welfare
Naveed Sattar - Institute of Cardiovascular and Medical Sciences
Dmitry Shungin - Lund University
Rona J. Strawbridge - Karolinska Institutet
Toshiko Tanaka - National Institutes of Health
Cornelia M. van Duijn - Department of Epidemiology
Ping An - Washington University in Saint Louis
Mariza de Andrade - Department of Health Sciences Research
Jeanette S. Andrews - Wake Forest University
Thor Aspelund - Icelandic Heart Association
Mustafa Atalay - Institute of Biomedicine, Physiology
Yurii Aulchenko - Department of Epidemiology
Beverley Balkau - Institut National de la Santé et de la Recherche Médicale
Stefania Bandinelli - Azienda Sanitaria Firenze
Jacques S. Beckmann - Department of Medical Genetics
John P. Beilby - Queen Elizabeth II Medical Centre
Claire Bellis - Research Institute
Richard N. Bergman - University of Southern California
John Blangero - 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 Institutes of Health
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Ingrid B. Borecki - Washington University in Saint Louis
Yvonne Boettcher - Leipzig University
Claude Bouchard - Pennington Biomedical Research Center
Eric Brunner - Department of Epidemiology & Public Health
Danijela Budimir - University of Split
Harry Campbell - University of Edinburgh
Olga Carlson - National Institutes of Health
Peter S. Chines - National Institutes of Health
Robert Clarke - University of Oxford
Francis S. Collins - National Institutes of Health
Arturo Corbatón-Anchuelo - San Carlos Clinical Hospital
David Couper - University of North Carolina
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 Institutes of Health
Johan G. Eriksson - University of Helsinki
Elodie Eury - Institut Pasteur
Luigi Ferrucci - National Institute on Aging
Ian Ford
Nita G. Forouhi
Caroline S. Fox
Maria Grazia Franzosi
Paul W. Franks
Timothy M. Frayling
Philippe Froguel - Institut Pasteur
Pilar Galan
Eco de Geus
Bruna Gigante - Karolinska Institutet
Nicole L. Glazer
Anuj Goel
Leif Groop
Vilmundur Gudnason - University of Iceland
Goeran Hallmans
Anders Hamsten
Ola Hansson
Tamara B. Harris
Caroline Hayward - University of Edinburgh
Simon Heath
Serge Hercberg - Unité de Recherche en Epidémiologie Nutritionnelle
Andrew A. Hicks
Aroon Hingorani
Albert Hofman - Department of Epidemiology
Jennie Hui
Joseph Hung
DIAGRAM Consortium
Publication Details: Nature genetics, Vol.44(6), pp.659-671
Publisher: Nature Publishing Group
Identifiers: 9934160708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article