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

Author:
  • 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
  • Loic Yengo
  • Cecile 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
  • Iva Miljkovic
  • Yongmei Liu
  • Mustafa Atalay
  • Wieland Kiess
  • Alan L. James
  • Fernando Rivadeneira
  • Andre G. Uitterlinden
  • Colin N. A. Palmer
  • Alex S. F. Doney
  • Gonneke Willemsen
  • Johannes H. Smit
  • Susan Campbell
  • Ozren Polasek
  • Lori L. Bonnycastle
  • Serge Hercberg
  • Maria Dimitriou
  • Jennifer L. Bolton
  • Gerard R. Fowkes
  • Peter Kovacs
  • Jaana Lindstrom
  • Tatijana Zemunik
  • Stefania Bandinelli
  • Sarah H. Wild
  • Hanneke V. Basart
  • Wolfgang Rathmann
  • Harald Grallert
  • Winfried Maerz
  • Marcus E. Kleber
  • Bernhard O. Boehm
  • Annette Peters
  • Peter P. Pramstaller
  • Michael A. Province
  • Ingrid B. Borecki
  • Nicholas D. Hastie
  • Igor Rudan
  • Harry Campbell
  • Hugh Watkins
  • Martin Farrall
  • Michael Stumvoll
  • Luigi Ferrucci
  • Dawn M. Waterworth
  • Richard N. Bergman
  • Francis S. Collins
  • Jaakko Tuomilehto
  • Richard M. Watanabe
  • Eco J. C. de Geus
  • Brenda W. Penninx
  • Albert Hofman
  • Ben A. Oostra
  • Bruce M. Psaty
  • Peter Vollenweider
  • James F. Wilson
  • Alan F. Wright
  • G. Kees Hovingh
  • Andres Metspalu
  • Matti Uusitupa
  • Patrik K. E. Magnusson
  • Kirsten O. Kyvik
  • Jaakko Kaprio
  • Jackie F. Price
  • George V. Dedoussis
  • Panos Deloukas
  • Pierre Meneton
  • Lars Lind
  • Michael Boehnke
  • Alan R. Shuldiner
  • Cornelia M. van Duijn
  • Andrew D. Morris
  • Anke Toenjes
  • Patricia A. Peyser
  • John P. Beilby
  • Antje Koerner
  • Johanna Kuusisto
  • Markku Laakso
  • Stefan R. Bornstein
  • Peter E. H. Schwarz
  • Timo A. Lakka
  • Rainer Rauramaa
  • Linda S. Adair
  • George Davey Smith
  • Tim D. Spector
  • Thomas Illig
  • Ulf de Faire
  • Anders Hamsten
  • Vilmundur Gudnason
  • Mika Kivimaki
  • Aroon Hingorani
  • Sirkka M. Keinanen-Kiukaanniemi
  • Timo E. Saaristo
  • Dorret I. Boomsma
  • Kari Stefansson
  • Pim van der Harst
  • Josee Dupuis
  • Nancy L. Pedersen
  • Naveed Sattar
  • Tamara B. Harris
  • Francesco Cucca
  • Samuli Ripatti
  • Veikko Salomaa
  • Karen L. Mohlke
  • Beverley Balkau
  • Philippe Froguel
  • Anneli Pouta
  • Marjo-Riitta Jarvelin
  • Nicholas J. Wareham
  • Nabila Bouatia-Naji
  • Mark I. McCarthy
  • Paul Franks
  • James B. Meigs
  • Tanya M. Teslovich
  • Jose C. Florez
  • Claudia Langenberg
  • Erik Ingelsson
  • Inga Prokopenko
  • Ines Barroso
Publishing year: 2012
Language: English
Pages: 991-991
Publication/Series: Nature Genetics
Volume: 44
Issue: 9
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • ISSN: 1546-1718
Paul Franks
E-mail: paul.franks [at] med.lu.se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00