Genetic Determinants of Habitual Physical Activity and Overweight and Obesity

We tested 6 single nucleotide polymorphisms (SNPs) associated with obesity from genome wide association studies for their association with physical activity (PA). Healthy European-American women (n=265) and men (n=230) (23.5±0.3yr, 24.6±0.2kg•m-2) were genotyped for MC4R (rs17782313), FTO (rs9939609), TMEM18 (rs6548238), NEGR1 (rs2815752), SH2B1 (rs7498665), and KCTD15 (rs11084753), and completed the Paffenbarger PA Questionnaire. We examined gene interactions by summing the number of obesity effect alleles. RESULTS: Normal weight subjects with MC4R T expended 1981.2±741.7kcal∙wk-1 less than non-carriers in total PA (p=0.008), 1825.9±650.2 kcal∙wk-1 less in sports/recreation (p=0.027), and 1231.3±552.7 kcal∙wk-1 less in vigorous PA (p=0.005). Subjects with TMEM18 C expended 1216.5±356.3kcal∙wk-1 lessthan non-carriers in moderate PA (p=0.001). Overweight men homozygous for FTO T expended 871.4±397.1kcal∙wk-1 less than A carriers in vigorous PA (p=0.031). Subjects homozygous for SH2B1 G spent 4.8±1.9hr∙wk-1 less than non-carriers in moderate PA (p=0.013), and 5.6±2.2hr∙wk-1 more in light PA. Women homozygous for NEGR1 G spent 7.6±2.7hr∙wk-1 less than A carriers in moderate PA (p=0.006). Overweight subjects homozygous for KCTD15 A spent 14.2 ±4.8hr∙wk-1 more than G carriers in sitting (p=0.004). Men with 5-6 (n=173) obesity effect alleles expanded 1082.3±447.2kcal∙wk-1 more in sports/recreation (p=0.049) and 663.8±418.1kcal∙wk-1 more in vigorous PA (p=0.049) than men with 7-10 (n=131), with similar non-significant trends noted for 1-4 (n=153) obesity effect alleles (p\u3e0.05). CONCLUSION: The genotype differences in energy expenditure that equate to 11-25 lb∙yr-1 have important implications for weight maintenance. The mechanisms explaining these associations appear to have a common central neural influence that should be explored further