Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study

Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study Ron Do 1 , Swneke D. Bailey 1 , Katia Desbiens 2 , Alexandre Belisle 3 , Alexandre Montpetit 3 , Claude Bouchard 4 , Louis Pérusse 5 6 , Marie-Claude Vohl 6 7 and James C. Engert 1 2 6 8 1 Department of Human Genetics, McGill University, Montréal, Québec, Canada 2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada 3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada 4 Pennington Biomedical Research Center, Baton Rouge, Louisiana 5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada 6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada 7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada 8 Department of Medicine, McGill University, Montréal, Québec, Canada Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca Abstract OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity. Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and expenditure. RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term study of extensively phenotyped individuals designed to investigate factors involved in adiposity. RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of