BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.
BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTOrs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.
Authors: Robert A Scott; Mark E S Bailey; Colin N Moran; Richard H Wilson; Noriyuki Fuku; Masashi Tanaka; Athanasios Tsiokanos; Athanasios Z Jamurtas; Evangelia Grammatikaki; George Moschonis; Yannis Manios; Yannis P Pitsiladis Journal: Eur J Hum Genet Date: 2010-08-18 Impact factor: 4.246
Authors: John E Blundell; Jennifer Lyn Baker; Emma Boyland; Ellen Blaak; Jadwiga Charzewska; Stefaan de Henauw; Gema Frühbeck; Marcela Gonzalez-Gross; Johannes Hebebrand; Lotte Holm; Vilma Kriaucioniene; Lauren Lissner; Jean-Michel Oppert; Karin Schindler; Ana Lúcia Silva; Euan Woodward Journal: Obes Facts Date: 2017-02-11 Impact factor: 3.942
Authors: Michael Fenech; Ahmed El-Sohemy; Leah Cahill; Lynnette R Ferguson; Tapaeru-Ariki C French; E Shyong Tai; John Milner; Woon-Puay Koh; Lin Xie; Michelle Zucker; Michael Buckley; Leah Cosgrove; Trevor Lockett; Kim Y C Fung; Richard Head Journal: J Nutrigenet Nutrigenomics Date: 2011-05-28
Authors: A S Richardson; K E North; M Graff; K M Young; K L Mohlke; L A Lange; E M Lange; K M Harris; P Gordon-Larsen Journal: Pediatr Obes Date: 2013-03-25 Impact factor: 4.000