AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/ INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/ INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Authors: Juliana C N Chan; Vasanti Malik; Weiping Jia; Takashi Kadowaki; Chittaranjan S Yajnik; Kun-Ho Yoon; Frank B Hu Journal: JAMA Date: 2009-05-27 Impact factor: 56.272
Authors: Seong W Cha; Sun M Choi; Kil S Kim; Byung L Park; Jae R Kim; Jong Y Kim; Hyoung D Shin Journal: Obesity (Silver Spring) Date: 2008-09 Impact factor: 5.002
Authors: F Takeuchi; K Yamamoto; T Katsuya; T Nabika; T Sugiyama; A Fujioka; M Isono; K Ohnaka; T Fujisawa; E Nakashima; H Ikegami; J Nakamura; Y Yamori; S Yamaguchi; S Kobayashi; T Ogihara; R Takayanagi; N Kato Journal: Diabetologia Date: 2011-03-03 Impact factor: 10.122
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
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Authors: Jonathan T Tan; Rajkumar Dorajoo; Mark Seielstad; Xue Ling Sim; Rick Twee-Hee Ong; Kee Seng Chia; Tien Yin Wong; Seang Mei Saw; Suok Kai Chew; Tin Aung; E-Shyong Tai Journal: Diabetes Date: 2008-07-03 Impact factor: 9.461
Authors: Mark M Iles; Matthew H Law; Simon N Stacey; Jiali Han; Shenying Fang; Ruth Pfeiffer; Mark Harland; Stuart Macgregor; John C Taylor; Katja K Aben; Lars A Akslen; Marie-Françoise Avril; Esther Azizi; Bert Bakker; Kristrun R Benediktsdottir; Wilma Bergman; Giovanna Bianchi Scarrà; Kevin M Brown; Donato Calista; Valérie Chaudru; Maria Concetta Fargnoli; Anne E Cust; Florence Demenais; Anne C de Waal; Tadeusz Dębniak; David E Elder; Eitan Friedman; Pilar Galan; Paola Ghiorzo; Elizabeth M Gillanders; Alisa M Goldstein; Nelleke A Gruis; Johan Hansson; Per Helsing; Marko Hočevar; Veronica Höiom; John L Hopper; Christian Ingvar; Marjolein Janssen; Mark A Jenkins; Peter A Kanetsky; Lambertus A Kiemeney; Julie Lang; G Mark Lathrop; Sancy Leachman; Jeffrey E Lee; Jan Lubiński; Rona M Mackie; Graham J Mann; Nicholas G Martin; Jose I Mayordomo; Anders Molven; Suzanne Mulder; Eduardo Nagore; Srdjan Novaković; Ichiro Okamoto; Jon H Olafsson; Håkan Olsson; Hubert Pehamberger; Ketty Peris; Maria Pilar Grasa; Dolores Planelles; Susana Puig; Joan Anton Puig-Butille; Juliette Randerson-Moor; Celia Requena; Licia Rivoltini; Monica Rodolfo; Mario Santinami; Bardur Sigurgeirsson; Helen Snowden; Fengju Song; Patrick Sulem; Kristin Thorisdottir; Rainer Tuominen; Patricia Van Belle; Nienke van der Stoep; Michelle M van Rossum; Qingyi Wei; Judith Wendt; Diana Zelenika; Mingfeng Zhang; Maria Teresa Landi; Gudmar Thorleifsson; D Timothy Bishop; Christopher I Amos; Nicholas K Hayward; Kari Stefansson; Julia A Newton Bishop; Jennifer H Barrett Journal: Nat Genet Date: 2013-03-03 Impact factor: 38.330