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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

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Authors

  • Josee Dupuis
  • Claudia Langenberg
  • Inga Prokopenko
  • Richa Saxena
  • Nicole Soranzo
  • Anne U. Jackson
  • Eleanor Wheeler
  • Nicole L. Glazer
  • Nabila Bouatia-Naji
  • Anna L. Gloyn
  • Cecilia M. Lindgren
  • Reedik Magi
  • Joshua Randall
  • Toby Johnson
  • Paul Elliott
  • Denis Rybin
  • Gudmar Thorleifsson
  • Valgerdur Steinthorsdottir
  • Peter Henneman
  • Harald Grallert
  • Abbas Dehghan
  • Jouke Jan Hottenga
  • Christopher S. Franklin
  • Pau Navarro
  • Kijoung Song
  • Anuj Goel
  • John R. B. Perry
  • Josephine M. Egan
  • Taina Lajunen
  • Niels Grarup
  • Thomas Sparso
  • Alex S. F. Doney
  • Benjamin F. Voight
  • Heather M. Stringham
  • Man Li
  • Stavroula Kanoni
  • Peter Shrader
  • Christine Cavalcanti-Proenca
  • Meena Kumari
  • Lu Qi
  • Nicholas J. Timpson
  • Christian Gieger
  • Carina Zabena
  • Ghislain Rocheleau
  • Erik Ingelsson
  • Ping An
  • Jeffrey O'Connell
  • Jian'an Luan
  • Amanda Elliott
  • Steven A. McCarroll
  • Felicity Payne
  • Rosa Maria Roccasecca
  • Francois Pattou
  • Praveen Sethupathy
  • Kristin Ardlie
  • Yavuz Ariyurek
  • Beverley Balkau
  • Philip Barter
  • John P. Beilby
  • Yoav Ben-Shlomo
  • Rafn Benediktsson
  • Amanda J. Bennett
  • Sven Bergmann
  • Murielle Bochud
  • Eric Boerwinkle
  • Amelie Bonnefond
  • Lori L. Bonnycastle
  • Knut Borch-Johnsen
  • Yvonne Boettcher
  • Eric Brunner
  • Suzannah J. Bumpstead
  • Guillaume Charpentier
  • Yii-Der Ida Chen
  • Peter Chines
  • Robert Clarke
  • Lachlan J. M. Coin
  • Matthew N. Cooper
  • Marilyn Cornelis
  • Gabe Crawford
  • Laura Crisponi
  • Ian N. M. Day
  • Eco J. C. de Geus
  • Jerome Delplanque
  • Christian Dina
  • Michael R. Erdos
  • Annette C. Fedson
  • Antje Fischer-Rosinsky
  • Nita G. Forouhi
  • Caroline S. Fox
  • Rune Frants
  • Maria Grazia Franzosi
  • Pilar Galan
  • Mark O. Goodarzi
  • Juergen Graessler
  • Christopher J. Groves
  • Scott Grundy
  • Rhian Gwilliam
  • Ulf Gyllensten
  • Samy Hadjadj
  • Goeran Hallmans
  • Naomi Hammond
  • Xijing Han
  • Anna-Liisa Hartikainen
  • Neelam Hassanali
  • Caroline Hayward
  • Simon C. Heath
  • Serge Hercberg
  • Christian Herder
  • Andrew A. Hicks
  • David R. Hillman
  • Aroon D. Hingorani
  • Albert Hofman
  • Jennie Hui
  • Joe Hung
  • Bo Isomaa
  • Paul R. V. Johnson
  • Torben Jorgensen
  • Antti Jula
  • Marika Kaakinen
  • Jaakko Kaprio
  • Y. Antero Kesaniemi
  • Mika Kivimaki
  • Beatrice Knight
  • Seppo Koskinen
  • Peter Kovacs
  • Kirsten Ohm Kyvik
  • G. Mark Lathrop
  • Debbie A. Lawlor
  • Olivier Le Bacquer
  • Cecile Lecoeur
  • Yun Li
  • Valeriya Lyssenko
  • Robert Mahley
  • Massimo Mangino
  • Alisa K. Manning
  • Maria Teresa Martinez-Larrad
  • Jarred B. McAteer
  • Laura J. McCulloch
  • Ruth McPherson
  • Christa Meisinger
  • David Melzer
  • David Meyre
  • Braxton D. Mitchell
  • Mario A. Morken
  • Sutapa Mukherjee
  • Silvia Naitza
  • Narisu Narisu
  • Matthew J. Neville
  • Ben A. Oostra
  • Marco Orru
  • Ruth Pakyz
  • Colin N. A. Palmer
  • Giuseppe Paolisso
  • Cristian Pattaro
  • Daniel Pearson
  • John F. Peden
  • Nancy L. Pedersen
  • Markus Perola
  • Andreas F. H. Pfeiffer
  • Irene Pichler
  • Ozren Polasek
  • Danielle Posthuma
  • Simon C. Potter
  • Anneli Pouta
  • Michael A. Province
  • Bruce M. Psaty
  • Wolfgang Rathmann
  • Nigel W. Rayner
  • Kenneth Rice
  • Samuli Ripatti
  • Fernando Rivadeneira
  • Michael Roden
  • Olov Rolandsson
  • Annelli Sandbaek
  • Manjinder Sandhu
  • Serena Sanna
  • Avan Aihie Sayer
  • Paul Scheet
  • Laura J. Scott
  • Udo Seedorf
  • Stephen J. Sharp
  • Beverley Shields
  • Gunnar Sigurosson
  • Eric J. G. Sijbrands
  • Angela Silveira
  • Laila Simpson
  • Andrew Singleton
  • Nicholas L. Smith
  • Ulla Sovio
  • Amy Swift
  • Holly Syddall
  • Ann-Christine Syvanen
  • Toshiko Tanaka
  • Barbara Thorand
  • Jean Tichet
  • Anke Tonjes
  • Tiinamaija Tuomi
  • Andre G. Uitterlinden
  • Ko Willems van Dijk
  • Mandy van Hoek
  • Dhiraj Varma
  • Sophie Visvikis-Siest
  • Veronique Vitart
  • Nicole Vogelzangs
  • Gerard Waeber
  • Peter J. Wagner
  • Andrew Walley
  • G. Bragi Walters
  • Kim L. Ward
  • Hugh Watkins
  • Michael N. Weedon
  • Sarah H. Wild
  • Gonneke Willemsen
  • Jaqueline C. M. Witteman
  • John W. G. Yarnell
  • Eleftheria Zeggini
  • Diana Zelenika
  • Bjorn Zethelius
  • Guangju Zhai
  • Jing Hua Zhao
  • M. Carola Zillikens
  • Ingrid B. Borecki
  • Ruth J. F. Loos
  • Pierre Meneton
  • Patrik K. E. Magnusson
  • David M. Nathan
  • Gordon H. Williams
  • Andrew T. Hattersley
  • Kaisa Silander
  • Veikko Salomaa
  • George Davey Smith
  • Stefan R. Bornstein
  • Peter Schwarz
  • Joachim Spranger
  • Fredrik Karpe
  • Alan R. Shuldiner
  • Cyrus Cooper
  • George V. Dedoussis
  • Manuel Serrano-Rios
  • Lars Lind
  • Lyle J. Palmer
  • Frank B. Hu
  • Paul W. Franks
  • Shah Ebrahim
  • Michael Marmot
  • W. H. Linda Kao
  • James S. Pankow
  • Michael J. Sampson
  • Johanna Kuusisto
  • Markku Laakso
  • Torben Hansen
  • Oluf Pedersen
  • Peter Paul Pramstaller
  • H. Erich Wichmann
  • Thomas Illig
  • Igor Rudan
  • Alan F. Wright
  • Michael Stumvoll
  • Harry Campbell
  • James F. Wilson
  • Richard N. Bergman
  • Thomas A. Buchanan
  • Francis S. Collins
  • Karen L. Mohlke
  • Jaakko Tuomilehto
  • Timo T. Valle
  • David Altshuler
  • Jerome I. Rotter
  • David S. Siscovick
  • Brenda W. J. H. Penninx
  • Dorret I. Boomsma
  • Panos Deloukas
  • Timothy D. Spector
  • Timothy M. Frayling
  • Luigi Ferrucci
  • Augustine Kong
  • Unnur Thorsteinsdottir
  • Kari Stefansson
  • Cornelia M. van Duijn
  • Yurii S. Aulchenko
  • Antonio Cao
  • Angelo Scuteri
  • David Schlessinger
  • Manuela Uda
  • Aimo Ruokonen
  • Marjo-Riitta Jarvelin
  • Dawn M. Waterworth
  • Peter Vollenweider
  • Leena Peltonen
  • Vincent Mooser
  • Goncalo R. Abecasis
  • Nicholas J. Wareham
  • Robert Sladek
  • Philippe Froguel
  • Richard M. Watanabe
  • James B. Meigs
  • Leif Groop
  • Michael Boehnke
  • Mark I. McCarthy
  • Jose C. Florez
  • Ines Barroso
  • Anders Hamsten Procardis Consortiu, Global BPgen Consortium, GIANT Consortium, DIAGRAM Consortium, MAGIC Investigators

Research units

Info

Original languageEnglish
Pages105-116
Number of pages12
JournalNature Genetics
Journal publication dateFeb 2010
Volume42
Issue2
DOIs
StatePublished
Peer-reviewedYes

Abstract

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

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