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

Robert A. Scott; Vasiliki Lagou; Ryan P. Welch; Eleanor Wheeler; May E. Montasser; Jian'An Luan; Reedik Maegi; Rona J. Strawbridge; Emil Rehnberg; Stefan Gustafsson; Stavroula Kanoni; Laura J. Rasmussen-Torvik; Loïc Yengo; Cécile Lecoeur; Dmitry Shungin; Serena Sanna; Carlo Sidore; Paul C. D. Johnson; J. Wouter Jukema; Toby Johnson; Anubha Mahajan; Niek Verweij; Gudmar Thorleifsson; Jouke-Jan Hottenga; Sonia Shah; Albert V. Smith; Bengt Sennblad; Christian Gieger; Perttu Salo; Markus Perola; Nicholas J. Timpson; David M. Evans; Beate St Pourcain; Ying Wu; Jeanette S. Andrews; Jennie Hui; Lawrence F. Bielak; Wei Zhao; Momoko Horikoshi; Pau Navarro; Aaron Isaacs; Jeffrey R. O'Connell; Kathleen Stirrups; Veronique Vitart; Caroline Hayward; Tonu Esko; Evelin Mihailov; Ross M. Fraser; Tove Fall; Benjamin F. Voight; Soumya Raychaudhuri; Han Chen; Cecilia M. Lindgren; Andrew P. Morris; Nigel W. Rayner; Neil Robertson; Denis Rybin; Ching-Ti Liu; Jacques S. Beckmann; Sara M. Willems; Peter S. Chines; Anne U. Jackson; Hyun Min Kang; Heather M. Stringham; Kijoung Song; Toshiko Tanaka; 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; DIAbet Genetics Replication; Inga Prokopenko

doi:10.1038/ng.2385

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

Journal article

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

Robert A. Scott, Vasiliki Lagou, Ryan P. Welch, Eleanor Wheeler, May E. Montasser, Jian'An Luan, Reedik Maegi, Rona J. Strawbridge, Emil Rehnberg, Stefan Gustafsson, …

Nature genetics, Vol.44(9), pp.991-+

01/09/2012

DOI: https://doi.org/10.1038/ng.2385

PMID: 22885924

Abstract

Life Sciences

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.

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Title: Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
Creators: Robert A. Scott - Addenbrooke's Hospital
Vasiliki Lagou - Wellcome Centre for Human Genetics
Ryan P. Welch - University of Michigan–Ann Arbor
Eleanor Wheeler - Wellcome Sanger Institute
May E. Montasser - University of Maryland, Baltimore
Jian'An Luan - Addenbrooke's Hospital
Reedik Maegi - Wellcome Trust
Rona J. Strawbridge - Karolinska Institutet
Emil Rehnberg - Karolinska Institutet
Stefan Gustafsson - Karolinska Institutet
Stavroula Kanoni - Wellcome Sanger Institute
Laura J. Rasmussen-Torvik - Northwestern University
Loïc Yengo - Université Lille Nord de France
Cécile Lecoeur - Université Lille Nord de France
Dmitry Shungin - Skåne University Hospital
Serena Sanna - Institute of Genetic and Biomedical Research
Carlo Sidore - University of Michigan–Ann Arbor
Paul C. D. Johnson - University of Glasgow
J. Wouter Jukema - Netherlands Heart Institute
Toby Johnson - William Harvey Research Institute
Anubha Mahajan - University of Oxford
Niek Verweij - University of Groningen
Gudmar Thorleifsson - deCODE Genetics
Jouke-Jan Hottenga - Vrije Universiteit Amsterdam
Sonia Shah - University College London
Albert V. Smith - Icelandic Heart Association
Bengt Sennblad - Karolinska Institutet
Christian Gieger - Helmholtz Zentrum München
Perttu Salo - Finnish Institute for Health and Welfare
Markus Perola - University of Tartu
Nicholas J. Timpson - University of Bristol
David M. Evans - University of Bristol
Beate St Pourcain
Ying Wu - North Carolina State University
Jeanette S. Andrews - Wake Forest University
Jennie Hui - Sir Charles Gairdner Hospital
Lawrence F. Bielak - University of Michigan–Ann Arbor
Wei Zhao - University of Michigan–Ann Arbor
Momoko Horikoshi - Oxford Centre for Diabetes, Endocrinology and Metabolism
Pau Navarro - MRC Institute of Genetics and Molecular Medicine
Aaron Isaacs - Centre for Medical Systems Biology
Jeffrey R. O'Connell - University of Maryland [College Park]
Kathleen Stirrups - Wellcome Sanger Institute
Veronique Vitart - University of Edinburgh
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Tonu Esko - University of Tartu
Evelin Mihailov - University of Tartu
Ross M. Fraser - University of Edinburgh
Tove Fall - Karolinska Institutet
Benjamin F. Voight - Broad Institute
Soumya Raychaudhuri - Brigham and Women's Hospital
Han Chen - Boston University
Cecilia M. Lindgren - University of Oxford
Andrew P. Morris - Wellcome Centre for Human Genetics
Nigel W. Rayner - Oxford Centre for Diabetes, Endocrinology and Metabolism
Neil Robertson - University of Oxford
Denis Rybin - Boston University
Ching-Ti Liu - Boston University
Jacques S. Beckmann - University of Lausanne
Sara M. Willems - Erasmus MC
Peter S. Chines - National Human Genome Research Institute
Anne U. Jackson - University of Michigan–Ann Arbor
Hyun Min Kang - University of Michigan–Ann Arbor
Heather M. Stringham - University of Michigan–Ann Arbor
Kijoung Song - GlaxoSmithKline
Toshiko Tanaka - National Institute on Aging
John F. Peden - Wellcome Centre for Human Genetics
Anuj Goel - University of Oxford
Andrew A. Hicks - Eurac Research
Ping An - Washington University in St. Louis
Martina Mueller-Nurasyid
Anders Franco-Cereceda
Lasse Folkersen - Karolinska University Hospital
Letizia Marullo - University of Oxford
Hanneke Jansen - University of Groningen
Albertine J. Oldehinkel - University Medical Center Groningen
Marcel Bruinenberg - University of Groningen
James S. Pankow - University of Minnesota
Kari E. North - University of North Carolina at Chapel Hill
Nita G. Forouhi - MRC Epidemiology Unit
Ruth J. F. Loos - MRC Epidemiology Unit
Sarah Edkins - Wellcome Sanger Institute
Tibor V. Varga - Skåne University Hospital
Goeran Hallmans
Heikki Oksa - Pirkanmaa Hospital District
Mulas Antonella
Ramaiah Nagaraja - National Institute on Aging
Stella Trompet - Netherlands Heart Institute
Ian Ford - University of Glasgow
Stephan J. L. Bakker - University Medical Center Groningen
Augustine Kong - deCODE Genetics
Meena Kumari - University College London
Bruna Gigante - Karolinska Institutet
Christian Herder - Deutsches Diabetes-Zentrum e.V.
Patricia B. Munroe - Queen Mary University of London
Mark Caulfield - Queen Mary University of London
Jula Antti - Finnish Institute for Health and Welfare
Massimo Mangino - King's College London
Kerrin Small - King's College London
Serge Hercberg - Inserm
DIAbet Genetics Replication
Inga Prokopenko - School of Biosciences
Publication Details: Nature genetics, Vol.44(9), pp.991-+
Publisher: Nature Publishing Group
Date published: 01/09/2012
Identifiers: 99928577602346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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