AIMS/HYPOTHESIS: There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. METHODS: We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK. RESULTS: We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p <or= 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99-1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09-1.21] per 0.28 SD increase in IL-18 levels). CONCLUSIONS/ INTERPRETATION: Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk, including type 1 diabetes, alter type 2 diabetes risk.
AIMS/HYPOTHESIS: There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. METHODS: We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK. RESULTS: We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p <or= 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99-1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09-1.21] per 0.28 SD increase in IL-18 levels). CONCLUSIONS/ INTERPRETATION: Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk, including type 1 diabetes, alter type 2 diabetes risk.
Authors: S Rafiq; T M Frayling; A Murray; A Hurst; K Stevens; M N Weedon; W Henley; L Ferrucci; S Bandinelli; A-M Corsi; J M Guralnik; D Melzer Journal: Genes Immun Date: 2007-08-02 Impact factor: 2.676
Authors: Robert M Plenge; Chris Cotsapas; Leela Davies; Alkes L Price; Paul I W de Bakker; Julian Maller; Itsik Pe'er; Noel P Burtt; Brendan Blumenstiel; Matt DeFelice; Melissa Parkin; Rachel Barry; Wendy Winslow; Claire Healy; Robert R Graham; Benjamin M Neale; Elena Izmailova; Ronenn Roubenoff; Alexander N Parker; Roberta Glass; Elizabeth W Karlson; Nancy Maher; David A Hafler; David M Lee; Michael F Seldin; Elaine F Remmers; Annette T Lee; Leonid Padyukov; Lars Alfredsson; Jonathan Coblyn; Michael E Weinblatt; Stacey B Gabriel; Shaun Purcell; Lars Klareskog; Peter K Gregersen; Nancy A Shadick; Mark J Daly; David Altshuler Journal: Nat Genet Date: 2007-11-04 Impact factor: 38.330
Authors: C Herder; N Klopp; J Baumert; M Müller; N Khuseyinova; C Meisinger; S Martin; T Illig; W Koenig; B Thorand Journal: Diabetologia Date: 2007-08-22 Impact factor: 10.122
Authors: Swapan K Nath; Shizhong Han; Xana Kim-Howard; Jennifer A Kelly; Parvathi Viswanathan; Gary S Gilkeson; Wei Chen; Cheng Zhu; Rodger P McEver; Robert P Kimberly; Marta E Alarcón-Riquelme; Timothy J Vyse; Quan-Zhen Li; Edward K Wakeland; Joan T Merrill; Judith A James; Kenneth M Kaufman; Joel M Guthridge; John B Harley Journal: Nat Genet Date: 2008-01-20 Impact factor: 38.330
Authors: John B Harley; Marta E Alarcón-Riquelme; Lindsey A Criswell; Chaim O Jacob; Robert P Kimberly; Kathy L Moser; Betty P Tsao; Timothy J Vyse; Carl D Langefeld; Swapan K Nath; Joel M Guthridge; Beth L Cobb; Daniel B Mirel; Miranda C Marion; Adrienne H Williams; Jasmin Divers; Wei Wang; Summer G Frank; Bahram Namjou; Stacey B Gabriel; Annette T Lee; Peter K Gregersen; Timothy W Behrens; Kimberly E Taylor; Michelle Fernando; Raphael Zidovetzki; Patrick M Gaffney; Jeffrey C Edberg; John D Rioux; Joshua O Ojwang; Judith A James; Joan T Merrill; Gary S Gilkeson; Michael F Seldin; Hong Yin; Emily C Baechler; Quan-Zhen Li; Edward K Wakeland; Gail R Bruner; Kenneth M Kaufman; Jennifer A Kelly Journal: Nat Genet Date: 2008-01-20 Impact factor: 38.330
Authors: Sergey V Kozyrev; Anna-Karin Abelson; Jerome Wojcik; Ammar Zaghlool; M V Prasad Linga Reddy; Elena Sanchez; Iva Gunnarsson; Elisabet Svenungsson; Gunnar Sturfelt; Andreas Jönsen; Lennart Truedsson; Bernardo A Pons-Estel; Torsten Witte; Sandra D'Alfonso; Nadia Barizzone; Nadia Barrizzone; Maria Giovanna Danieli; Carmen Gutierrez; Ana Suarez; Peter Junker; Helle Laustrup; Maria Francisca González-Escribano; Javier Martin; Hadi Abderrahim; Marta E Alarcón-Riquelme Journal: Nat Genet Date: 2008-01-20 Impact factor: 38.330
Authors: David A Hafler; Alastair Compston; Stephen Sawcer; Eric S Lander; Mark J Daly; Philip L De Jager; Paul I W de Bakker; Stacey B Gabriel; Daniel B Mirel; Adrian J Ivinson; Margaret A Pericak-Vance; Simon G Gregory; John D Rioux; Jacob L McCauley; Jonathan L Haines; Lisa F Barcellos; Bruce Cree; Jorge R Oksenberg; Stephen L Hauser Journal: N Engl J Med Date: 2007-07-29 Impact factor: 91.245
Authors: Christopher E Lowe; Jason D Cooper; Todd Brusko; Neil M Walker; Deborah J Smyth; Rebecca Bailey; Kirsi Bourget; Vincent Plagnol; Sarah Field; Mark Atkinson; David G Clayton; Linda S Wicker; John A Todd Journal: Nat Genet Date: 2007-08-05 Impact factor: 38.330
Authors: Paul R Burton; David G Clayton; Lon R Cardon; Nick Craddock; Panos Deloukas; Audrey Duncanson; Dominic P Kwiatkowski; Mark I McCarthy; Willem H Ouwehand; Nilesh J Samani; John A Todd; Peter Donnelly; Jeffrey C Barrett; Dan Davison; Doug Easton; David M Evans; Hin-Tak Leung; Jonathan L Marchini; Andrew P Morris; Chris C A Spencer; Martin D Tobin; Antony P Attwood; James P Boorman; Barbara Cant; Ursula Everson; Judith M Hussey; Jennifer D Jolley; Alexandra S Knight; Kerstin Koch; Elizabeth Meech; Sarah Nutland; Christopher V Prowse; Helen E Stevens; Niall C Taylor; Graham R Walters; Neil M Walker; Nicholas A Watkins; Thilo Winzer; Richard W Jones; Wendy L McArdle; Susan M Ring; David P Strachan; Marcus Pembrey; Gerome Breen; David St Clair; Sian Caesar; Katharine Gordon-Smith; Lisa Jones; Christine Fraser; Elaine K Green; Detelina Grozeva; Marian L Hamshere; Peter A Holmans; Ian R Jones; George Kirov; Valentina Moskivina; Ivan Nikolov; Michael C O'Donovan; Michael J Owen; David A Collier; Amanda Elkin; Anne Farmer; Richard Williamson; Peter McGuffin; Allan H Young; I Nicol Ferrier; Stephen G Ball; Anthony J Balmforth; Jennifer H Barrett; Timothy D Bishop; Mark M Iles; Azhar Maqbool; Nadira Yuldasheva; Alistair S Hall; Peter S Braund; Richard J Dixon; Massimo Mangino; Suzanne Stevens; John R Thompson; Francesca Bredin; Mark Tremelling; Miles Parkes; Hazel Drummond; Charles W Lees; Elaine R Nimmo; Jack Satsangi; Sheila A Fisher; Alastair Forbes; Cathryn M Lewis; Clive M Onnie; Natalie J Prescott; Jeremy Sanderson; Christopher G Matthew; Jamie Barbour; M Khalid Mohiuddin; Catherine E Todhunter; John C Mansfield; Tariq Ahmad; Fraser R Cummings; Derek P Jewell; John Webster; Morris J Brown; Mark G Lathrop; John Connell; Anna Dominiczak; Carolina A Braga Marcano; Beverley Burke; Richard Dobson; Johannie Gungadoo; Kate L Lee; Patricia B Munroe; Stephen J Newhouse; Abiodun Onipinla; Chris Wallace; Mingzhan Xue; Mark Caulfield; Martin Farrall; Anne Barton; Ian N Bruce; Hannah Donovan; Steve Eyre; Paul D Gilbert; Samantha L Hilder; Anne M Hinks; Sally L John; Catherine Potter; Alan J Silman; Deborah P M Symmons; Wendy Thomson; Jane Worthington; David B Dunger; Barry Widmer; Timothy M Frayling; Rachel M Freathy; Hana Lango; John R B Perry; Beverley M Shields; Michael N Weedon; Andrew T Hattersley; Graham A Hitman; Mark Walker; Kate S Elliott; Christopher J Groves; Cecilia M Lindgren; Nigel W Rayner; Nicolas J Timpson; Eleftheria Zeggini; Melanie Newport; Giorgio Sirugo; Emily Lyons; Fredrik Vannberg; Adrian V S Hill; Linda A Bradbury; Claire Farrar; Jennifer J Pointon; Paul Wordsworth; Matthew A Brown; Jayne A Franklyn; Joanne M Heward; Matthew J Simmonds; Stephen C L Gough; Sheila Seal; Michael R Stratton; Nazneen Rahman; Maria Ban; An Goris; Stephen J Sawcer; Alastair Compston; David Conway; Muminatou Jallow; Melanie Newport; Giorgio Sirugo; Kirk A Rockett; Suzannah J Bumpstead; Amy Chaney; Kate Downes; Mohammed J R Ghori; Rhian Gwilliam; Sarah E Hunt; Michael Inouye; Andrew Keniry; Emma King; Ralph McGinnis; Simon Potter; Rathi Ravindrarajah; Pamela Whittaker; Claire Widden; David Withers; Niall J Cardin; Dan Davison; Teresa Ferreira; Joanne Pereira-Gale; Ingeleif B Hallgrimsdo'ttir; Bryan N Howie; Zhan Su; Yik Ying Teo; Damjan Vukcevic; David Bentley; Matthew A Brown; Alastair Compston; Martin Farrall; Alistair S Hall; Andrew T Hattersley; Adrian V S Hill; Miles Parkes; Marcus Pembrey; Michael R Stratton; Sarah L Mitchell; Paul R Newby; Oliver J Brand; Jackie Carr-Smith; Simon H S Pearce; R McGinnis; A Keniry; P Deloukas; John D Reveille; Xiaodong Zhou; Anne-Marie Sims; Alison Dowling; Jacqueline Taylor; Tracy Doan; John C Davis; Laurie Savage; Michael M Ward; Thomas L Learch; Michael H Weisman; Mathew Brown Journal: Nat Genet Date: 2007-10-21 Impact factor: 38.330
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Authors: Gary W Beecham; Eden R Martin; John R Gilbert; Jonathan L Haines; Margaret A Pericak-Vance Journal: Ann Hum Genet Date: 2010-05 Impact factor: 1.670
Authors: J R B Perry; L Ferrucci; S Bandinelli; J Guralnik; R D Semba; N Rice; D Melzer; R Saxena; L J Scott; M I McCarthy; A T Hattersley; E Zeggini; M N Weedon; T M Frayling Journal: Diabetologia Date: 2009-08-07 Impact factor: 10.122
Authors: Kyra J Becker; Dorender Dankwa; Richard Lee; Juliane Schulze; Dannielle Zierath; Patricia Tanzi; Kevin Cain; Alexander Dressel; Dean Shibata; Jonathan Weinstein Journal: Neurocrit Care Date: 2014-08 Impact factor: 3.210
Authors: J Brent Richards; Dawn Waterworth; Stephen O'Rahilly; Marie-France Hivert; Ruth J F Loos; John R B Perry; Toshiko Tanaka; Nicholas John Timpson; Robert K Semple; Nicole Soranzo; Kijoung Song; Nuno Rocha; Elin Grundberg; Josée Dupuis; Jose C Florez; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Robert Sladek; Yurii Aulchenko; David Evans; Gerard Waeber; Jeanette Erdmann; Mary-Susan Burnett; Naveed Sattar; Joseph Devaney; Christina Willenborg; Aroon Hingorani; Jaquelin C M Witteman; Peter Vollenweider; Beate Glaser; Christian Hengstenberg; Luigi Ferrucci; David Melzer; Klaus Stark; John Deanfield; Janina Winogradow; Martina Grassl; Alistair S Hall; Josephine M Egan; John R Thompson; Sally L Ricketts; Inke R König; Wibke Reinhard; Scott Grundy; H-Erich Wichmann; Phil Barter; Robert Mahley; Y Antero Kesaniemi; Daniel J Rader; Muredach P Reilly; Stephen E Epstein; Alexandre F R Stewart; Cornelia M Van Duijn; Heribert Schunkert; Keith Burling; Panos Deloukas; Tomi Pastinen; Nilesh J Samani; Ruth McPherson; George Davey Smith; Timothy M Frayling; Nicholas J Wareham; James B Meigs; Vincent Mooser; Tim D Spector Journal: PLoS Genet Date: 2009-12-11 Impact factor: 5.917
Authors: John R B Perry; Michael N Weedon; Claudia Langenberg; Anne U Jackson; Valeriya Lyssenko; Thomas Sparsø; Gudmar Thorleifsson; Harald Grallert; Luigi Ferrucci; Marcello Maggio; Giuseppe Paolisso; Mark Walker; Colin N A Palmer; Felicity Payne; Elizabeth Young; Christian Herder; Narisu Narisu; Mario A Morken; Lori L Bonnycastle; Katharine R Owen; Beverley Shields; Beatrice Knight; Amanda Bennett; Christopher J Groves; Aimo Ruokonen; Marjo Riitta Jarvelin; Ewan Pearson; Laura Pascoe; Ele Ferrannini; Stefan R Bornstein; Heather M Stringham; Laura J Scott; Johanna Kuusisto; Peter Nilsson; Malin Neptin; Anette P Gjesing; Charlotta Pisinger; Torsten Lauritzen; Annelli Sandbaek; Mike Sampson; Ele Zeggini; Cecilia M Lindgren; Valgerdur Steinthorsdottir; Unnur Thorsteinsdottir; Torben Hansen; Peter Schwarz; Thomas Illig; Markku Laakso; Kari Stefansson; Andrew D Morris; Leif Groop; Oluf Pedersen; Michael Boehnke; Inês Barroso; Nicholas J Wareham; Andrew T Hattersley; Mark I McCarthy; Timothy M Frayling Journal: Hum Mol Genet Date: 2009-11-18 Impact factor: 6.150
Authors: S M Raj; J M M Howson; N M Walker; J D Cooper; D J Smyth; S F Field; H E Stevens; J A Todd Journal: Diabetologia Date: 2009-05-20 Impact factor: 10.122