OBJECTIVE: Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk. METHODS: We retrieved published literature from PubMed and Embase. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- or random-effect models. RESULTS: In the meta-analysis of 42 studies for 11 obesity/BMI-associated loci, we observed a statistically significant association of the FTO rs9939609 polymorphism (66 425 T2D cases/239 689 normoglycaemic subjects; P = 1·00 × 10(-41) ) and six other variants with T2D risk (17 915 T2D cases/27 531 normoglycaemic individuals: n = 40 629-130 001; all P < 0·001 for SH2B1 rs7498665, FAIM2 rs7138803, TMEM18 rs7561317, GNPDA2 rs10938397, BDNF rs925946 and NEGR1 rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all P < 0·05 for FTO rs9939609, SH2B1 rs7498665, FAIM2 rs7138803, GNPDA2 rs10938397). Subgroup analysis by ethnicity demonstrated similar results. CONCLUSIONS: This meta-analysis indicates that several BMI-associated variants are significantly associated with T2D risk. Some variants increase the T2D risk independent of obesity, while others mediate this risk through obesity.
OBJECTIVE: Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk. METHODS: We retrieved published literature from PubMed and Embase. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- or random-effect models. RESULTS: In the meta-analysis of 42 studies for 11 obesity/BMI-associated loci, we observed a statistically significant association of the FTOrs9939609 polymorphism (66 425 T2D cases/239 689 normoglycaemic subjects; P = 1·00 × 10(-41) ) and six other variants with T2D risk (17 915 T2D cases/27 531 normoglycaemic individuals: n = 40 629-130 001; all P < 0·001 for SH2B1rs7498665, FAIM2rs7138803, TMEM18rs7561317, GNPDA2rs10938397, BDNFrs925946 and NEGR1rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all P < 0·05 for FTOrs9939609, SH2B1rs7498665, FAIM2rs7138803, GNPDA2rs10938397). Subgroup analysis by ethnicity demonstrated similar results. CONCLUSIONS: This meta-analysis indicates that several BMI-associated variants are significantly associated with T2D risk. Some variants increase the T2D risk independent of obesity, while others mediate this risk through obesity.
Authors: C Herder; W Rathmann; K Strassburger; H Finner; H Grallert; C Huth; C Meisinger; C Gieger; S Martin; G Giani; W A Scherbaum; H-E Wichmann; T Illig Journal: Horm Metab Res Date: 2008-07-02 Impact factor: 2.936
Authors: Jie Wen; Tina Rönn; Anders Olsson; Zhen Yang; Bin Lu; Yieping Du; Leif Groop; Charlotte Ling; Renming Hu Journal: PLoS One Date: 2010-02-10 Impact factor: 3.240
Authors: C S Yajnik; C S Janipalli; S Bhaskar; S R Kulkarni; R M Freathy; S Prakash; K R Mani; M N Weedon; S D Kale; J Deshpande; G V Krishnaveni; S R Veena; C H D Fall; M I McCarthy; T M Frayling; A T Hattersley; G R Chandak Journal: Diabetologia Date: 2008-11-13 Impact factor: 10.122
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: Angelo Scuteri; Serena Sanna; Wei-Min Chen; Manuela Uda; Giuseppe Albai; James Strait; Samer Najjar; Ramaiah Nagaraja; Marco Orrú; Gianluca Usala; Mariano Dei; Sandra Lai; Andrea Maschio; Fabio Busonero; Antonella Mulas; Georg B Ehret; Ashley A Fink; Alan B Weder; Richard S Cooper; Pilar Galan; Aravinda Chakravarti; David Schlessinger; Antonio Cao; Edward Lakatta; Gonçalo R Abecasis Journal: PLoS Genet Date: 2007-07 Impact factor: 5.917
Authors: Dharambir K Sanghera; Lyda Ortega; Shizhong Han; Jairup Singh; Sarju K Ralhan; Gurpreet S Wander; Narinder K Mehra; John J Mulvihill; Robert E Ferrell; Swapan K Nath; Mohammed I Kamboh Journal: BMC Med Genet Date: 2008-07-03 Impact factor: 2.103
Authors: Cristen J Willer; Elizabeth K Speliotes; Ruth J F Loos; Shengxu Li; Cecilia M Lindgren; Iris M Heid; Sonja I Berndt; Amanda L Elliott; Anne U Jackson; Claudia Lamina; Guillaume Lettre; Noha Lim; Helen N Lyon; Steven A McCarroll; Konstantinos Papadakis; Lu Qi; Joshua C Randall; Rosa Maria Roccasecca; Serena Sanna; Paul Scheet; Michael N Weedon; Eleanor Wheeler; Jing Hua Zhao; Leonie C Jacobs; Inga Prokopenko; Nicole Soranzo; Toshiko Tanaka; Nicholas J Timpson; Peter Almgren; Amanda Bennett; Richard N Bergman; Sheila A Bingham; Lori L Bonnycastle; Morris Brown; Noël P Burtt; Peter Chines; Lachlan Coin; Francis S Collins; John M Connell; Cyrus Cooper; George Davey Smith; Elaine M Dennison; Parimal Deodhar; Paul Elliott; Michael R Erdos; Karol Estrada; David M Evans; Lauren Gianniny; Christian Gieger; Christopher J Gillson; Candace Guiducci; Rachel Hackett; David Hadley; Alistair S Hall; Aki S Havulinna; Johannes Hebebrand; Albert Hofman; Bo Isomaa; Kevin B Jacobs; Toby Johnson; Pekka Jousilahti; Zorica Jovanovic; Kay-Tee Khaw; Peter Kraft; Mikko Kuokkanen; Johanna Kuusisto; Jaana Laitinen; Edward G Lakatta; Jian'an Luan; Robert N Luben; Massimo Mangino; Wendy L McArdle; Thomas Meitinger; Antonella Mulas; Patricia B Munroe; Narisu Narisu; Andrew R Ness; Kate Northstone; Stephen O'Rahilly; Carolin Purmann; Matthew G Rees; Martin Ridderstråle; Susan M Ring; Fernando Rivadeneira; Aimo Ruokonen; Manjinder S Sandhu; Jouko Saramies; Laura J Scott; Angelo Scuteri; Kaisa Silander; Matthew A Sims; Kijoung Song; Jonathan Stephens; Suzanne Stevens; Heather M Stringham; Y C Loraine Tung; Timo T Valle; Cornelia M Van Duijn; Karani S Vimaleswaran; Peter Vollenweider; Gerard Waeber; Chris Wallace; Richard M Watanabe; Dawn M Waterworth; Nicholas Watkins; Jacqueline C M Witteman; Eleftheria Zeggini; Guangju Zhai; M Carola Zillikens; David Altshuler; Mark J Caulfield; Stephen J Chanock; I Sadaf Farooqi; Luigi Ferrucci; Jack M Guralnik; Andrew T Hattersley; Frank B Hu; Marjo-Riitta Jarvelin; Markku Laakso; Vincent Mooser; Ken K Ong; Willem H Ouwehand; Veikko Salomaa; Nilesh J Samani; Timothy D Spector; Tiinamaija Tuomi; Jaakko Tuomilehto; Manuela Uda; André G Uitterlinden; Nicholas J Wareham; Panagiotis Deloukas; Timothy M Frayling; Leif C Groop; Richard B Hayes; David J Hunter; Karen L Mohlke; Leena Peltonen; David Schlessinger; David P Strachan; H-Erich Wichmann; Mark I McCarthy; Michael Boehnke; Inês Barroso; Gonçalo R Abecasis; Joel N Hirschhorn Journal: Nat Genet Date: 2008-12-14 Impact factor: 38.330
Authors: Denise Anderson; Heather J Cordell; Michaela Fakiola; Richard W Francis; Genevieve Syn; Elizabeth S H Scaman; Elizabeth Davis; Simon J Miles; Toby McLeay; Sarra E Jamieson; Jenefer M Blackwell Journal: PLoS One Date: 2015-03-11 Impact factor: 3.240
Authors: Robert M Cronin; Julie R Field; Yuki Bradford; Christian M Shaffer; Robert J Carroll; Jonathan D Mosley; Lisa Bastarache; Todd L Edwards; Scott J Hebbring; Simon Lin; Lucia A Hindorff; Paul K Crane; Sarah A Pendergrass; Marylyn D Ritchie; Dana C Crawford; Jyotishman Pathak; Suzette J Bielinski; David S Carrell; David R Crosslin; David H Ledbetter; David J Carey; Gerard Tromp; Marc S Williams; Eric B Larson; Gail P Jarvik; Peggy L Peissig; Murray H Brilliant; Catherine A McCarty; Christopher G Chute; Iftikhar J Kullo; Erwin Bottinger; Rex Chisholm; Maureen E Smith; Dan M Roden; Joshua C Denny Journal: Front Genet Date: 2014-08-05 Impact factor: 4.599
Authors: Joo-Yeon Hwang; Hyo Jung Lee; Min Jin Go; Han Byul Jang; Nak-Hyun Choi; Jae Bum Bae; Juan E Castillo-Fernandez; Jordana T Bell; Tim D Spector; Hye-Ja Lee; Bong-Jo Kim Journal: Sci Rep Date: 2018-10-05 Impact factor: 4.379