AIMS/HYPOTHESIS: Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes. METHODS: We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype. RESULTS: The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 × 10(-4)), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings. CONCLUSIONS/ INTERPRETATION: Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes.
AIMS/HYPOTHESIS: Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes. METHODS: We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype. RESULTS: The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 × 10(-4)), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings. CONCLUSIONS/ INTERPRETATION: Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes.
Authors: David M Nathan; Mayer B Davidson; Ralph A DeFronzo; Robert J Heine; Robert R Henry; Richard Pratley; Bernard Zinman Journal: Diabetes Care Date: 2007-03 Impact factor: 19.112
Authors: M J Groenewoud; J M Dekker; A Fritsche; E Reiling; G Nijpels; R J Heine; J A Maassen; F Machicao; S A Schäfer; H U Häring; L M 't Hart; T W van Haeften Journal: Diabetologia Date: 2008-07-11 Impact factor: 10.122
Authors: Richa Saxena; Benjamin F Voight; Valeriya Lyssenko; Noël P Burtt; Paul I W de Bakker; Hong Chen; Jeffrey J Roix; Sekar Kathiresan; Joel N Hirschhorn; Mark J Daly; Thomas E Hughes; Leif Groop; David Altshuler; Peter Almgren; Jose C Florez; Joanne Meyer; Kristin Ardlie; Kristina Bengtsson Boström; Bo Isomaa; Guillaume Lettre; Ulf Lindblad; Helen N Lyon; Olle Melander; Christopher Newton-Cheh; Peter Nilsson; Marju Orho-Melander; Lennart Råstam; Elizabeth K Speliotes; Marja-Riitta Taskinen; Tiinamaija Tuomi; Candace Guiducci; Anna Berglund; Joyce Carlson; Lauren Gianniny; Rachel Hackett; Liselotte Hall; Johan Holmkvist; Esa Laurila; Marketa Sjögren; Maria Sterner; Aarti Surti; Margareta Svensson; Malin Svensson; Ryan Tewhey; Brendan Blumenstiel; Melissa Parkin; Matthew Defelice; Rachel Barry; Wendy Brodeur; Jody Camarata; Nancy Chia; Mary Fava; John Gibbons; Bob Handsaker; Claire Healy; Kieu Nguyen; Casey Gates; Carrie Sougnez; Diane Gage; Marcia Nizzari; Stacey B Gabriel; Gung-Wei Chirn; Qicheng Ma; Hemang Parikh; Delwood Richardson; Darrell Ricke; Shaun Purcell Journal: Science Date: 2007-04-26 Impact factor: 47.728
Authors: A R Folsom; D R Jacobs; L E Wagenknecht; S P Winkhart; C Yunis; J E Hilner; P J Savage; D E Smith; J M Flack Journal: Am J Epidemiol Date: 1996-08-01 Impact factor: 4.897
Authors: Eleftheria Zeggini; Michael N Weedon; Cecilia M Lindgren; Timothy M Frayling; Katherine S Elliott; Hana Lango; Nicholas J Timpson; John R B Perry; Nigel W Rayner; Rachel M Freathy; Jeffrey C Barrett; Beverley Shields; Andrew P Morris; Sian Ellard; Christopher J Groves; Lorna W Harries; Jonathan L Marchini; Katharine R Owen; Beatrice Knight; Lon R Cardon; Mark Walker; Graham A Hitman; Andrew D Morris; Alex S F Doney; Mark I McCarthy; Andrew T Hattersley Journal: Science Date: 2007-04-26 Impact factor: 47.728
Authors: Manjinder S Sandhu; Michael N Weedon; Katherine A Fawcett; Jon Wasson; Sally L Debenham; Allan Daly; Hana Lango; Timothy M Frayling; Rosalind J Neumann; Richard Sherva; Ilana Blech; Paul D Pharoah; Colin N A Palmer; Charlotte Kimber; Roger Tavendale; Andrew D Morris; Mark I McCarthy; Mark Walker; Graham Hitman; Benjamin Glaser; M Alan Permutt; Andrew T Hattersley; Nicholas J Wareham; Inês Barroso Journal: Nat Genet Date: 2007-07-01 Impact factor: 38.330
Authors: Brendan J Keating; Sam Tischfield; Sarah S Murray; Tushar Bhangale; Thomas S Price; Joseph T Glessner; Luana Galver; Jeffrey C Barrett; Struan F A Grant; Deborah N Farlow; Hareesh R Chandrupatla; Mark Hansen; Saad Ajmal; George J Papanicolaou; Yiran Guo; Mingyao Li; Stephanie Derohannessian; Paul I W de Bakker; Swneke D Bailey; Alexandre Montpetit; Andrew C Edmondson; Kent Taylor; Xiaowu Gai; Susanna S Wang; Myriam Fornage; Tamim Shaikh; Leif Groop; Michael Boehnke; Alistair S Hall; Andrew T Hattersley; Edward Frackelton; Nick Patterson; Charleston W K Chiang; Cecelia E Kim; Richard R Fabsitz; Willem Ouwehand; Alkes L Price; Patricia Munroe; Mark Caulfield; Thomas Drake; Eric Boerwinkle; David Reich; A Stephen Whitehead; Thomas P Cappola; Nilesh J Samani; A Jake Lusis; Eric Schadt; James G Wilson; Wolfgang Koenig; Mark I McCarthy; Sekar Kathiresan; Stacey B Gabriel; Hakon Hakonarson; Sonia S Anand; Muredach Reilly; James C Engert; Deborah A Nickerson; Daniel J Rader; Joel N Hirschhorn; Garret A Fitzgerald Journal: PLoS One Date: 2008-10-31 Impact factor: 3.240
Authors: Marta Garaulet; Purificación Gómez-Abellán; Patricia Rubio-Sastre; Juan A Madrid; Richa Saxena; Frank A J L Scheer Journal: Metabolism Date: 2015-08-14 Impact factor: 8.694
Authors: N Franceschini; K Haack; H H H Göring; V S Voruganti; S Laston; L Almasy; E T Lee; L G Best; R R Fabsitz; K E North; J W Maccluer; J B Meigs; J S Pankow; S A Cole Journal: Diabetologia Date: 2013-07-14 Impact factor: 10.122
Authors: Su Yon Jung; Eric M Sobel; Jeanette C Papp; Carolyn J Crandall; Alan N Fu; Zuo-Feng Zhang Journal: Genet Epidemiol Date: 2016-07-05 Impact factor: 2.135
Authors: Marta Garaulet; Jingyi Qian; Jose C Florez; Josephine Arendt; Richa Saxena; Frank A J L Scheer Journal: Trends Endocrinol Metab Date: 2020-01-01 Impact factor: 12.015
Authors: Folkert W Asselbergs; Yiran Guo; Erik P A van Iperen; Suthesh Sivapalaratnam; Vinicius Tragante; Matthew B Lanktree; Leslie A Lange; Berta Almoguera; Yolande E Appelman; John Barnard; Jens Baumert; Amber L Beitelshees; Tushar R Bhangale; Yii-Der Ida Chen; Tom R Gaunt; Yan Gong; Jemma C Hopewell; Toby Johnson; Marcus E Kleber; Taimour Y Langaee; Mingyao Li; Yun R Li; Kiang Liu; Caitrin W McDonough; Matthijs F L Meijs; Rita P S Middelberg; Kiran Musunuru; Christopher P Nelson; Jeffery R O'Connell; Sandosh Padmanabhan; James S Pankow; Nathan Pankratz; Suzanne Rafelt; Ramakrishnan Rajagopalan; Simon P R Romaine; Nicholas J Schork; Jonathan Shaffer; Haiqing Shen; Erin N Smith; Sam E Tischfield; Peter J van der Most; Jana V van Vliet-Ostaptchouk; Niek Verweij; Kelly A Volcik; Li Zhang; Kent R Bailey; Kristian M Bailey; Florianne Bauer; Jolanda M A Boer; Peter S Braund; Amber Burt; Paul R Burton; Sarah G Buxbaum; Wei Chen; Rhonda M Cooper-Dehoff; L Adrienne Cupples; Jonas S deJong; Christian Delles; David Duggan; Myriam Fornage; Clement E Furlong; Nicole Glazer; John G Gums; Claire Hastie; Michael V Holmes; Thomas Illig; Susan A Kirkland; Mika Kivimaki; Ronald Klein; Barbara E Klein; Charles Kooperberg; Kandice Kottke-Marchant; Meena Kumari; Andrea Z LaCroix; Laya Mallela; Gurunathan Murugesan; Jose Ordovas; Willem H Ouwehand; Wendy S Post; Richa Saxena; Hubert Scharnagl; Pamela J Schreiner; Tina Shah; Denis C Shields; Daichi Shimbo; Sathanur R Srinivasan; Ronald P Stolk; Daniel I Swerdlow; Herman A Taylor; Eric J Topol; Elina Toskala; Joost L van Pelt; Jessica van Setten; Salim Yusuf; John C Whittaker; A H Zwinderman; Sonia S Anand; Anthony J Balmforth; Gerald S Berenson; Connie R Bezzina; Bernhard O Boehm; Eric Boerwinkle; Juan P Casas; Mark J Caulfield; Robert Clarke; John M Connell; Karen J Cruickshanks; Karina W Davidson; Ian N M Day; Paul I W de Bakker; Pieter A Doevendans; Anna F Dominiczak; Alistair S Hall; Catharina A Hartman; Christian Hengstenberg; Hans L Hillege; Marten H Hofker; Steve E Humphries; Gail P Jarvik; Julie A Johnson; Bernhard M Kaess; Sekar Kathiresan; Wolfgang Koenig; Debbie A Lawlor; Winfried März; Olle Melander; Braxton D Mitchell; Grant W Montgomery; Patricia B Munroe; Sarah S Murray; Stephen J Newhouse; N Charlotte Onland-Moret; Neil Poulter; Bruce Psaty; Susan Redline; Stephen S Rich; Jerome I Rotter; Heribert Schunkert; Peter Sever; Alan R Shuldiner; Roy L Silverstein; Alice Stanton; Barbara Thorand; Mieke D Trip; Michael Y Tsai; Pim van der Harst; Ellen van der Schoot; Yvonne T van der Schouw; W M Monique Verschuren; Hugh Watkins; Arthur A M Wilde; Bruce H R Wolffenbuttel; John B Whitfield; G Kees Hovingh; Christie M Ballantyne; Cisca Wijmenga; Muredach P Reilly; Nicholas G Martin; James G Wilson; Daniel J Rader; Nilesh J Samani; Alex P Reiner; Robert A Hegele; John J P Kastelein; Aroon D Hingorani; Philippa J Talmud; Hakon Hakonarson; Clara C Elbers; Brendan J Keating; Fotios Drenos Journal: Am J Hum Genet Date: 2012-10-11 Impact factor: 11.025