PURPOSE: Genetic factors account for 40%-70% of the population variation in body mass index (BMI), suggesting that genetic predisposition is a major risk factor for excess weight. The purpose of this study was to test whether exercise attenuates the inherited risk for excess body weight. METHODS: Survey questionnaires of exercise (usual running distance) and BMI were obtained from a national sample of 582 female and 344 male self-identified monozygotic (MZ) twins. Regression analyses were used to test whether running disparity diminished the inheritance of BMI when adjusted for age, education, cigarette use, and selected dietary variables. RESULTS: The active twins ran between 0 and 10.7 km . d(-1) more than their less active twins if female (mean +/- SD = 1.61 +/- 1.50 km . d(-1)) and between 0 and 13.7 km . d(-1) more if male (1.88 +/- 1.78 km . d(-1)). Average BMIs of the less active twins were 22.38 +/- 3.56 and 24.59 +/- 3.08 kg . m(-2) in females and males, respectively. Within-twin correlations were significant (P < 0.0001) for usual distance run (females: r = 0.64; males: r = 0.61) and BMI (females: r = 0.67; males: r = 0.71). Greater running differences (Deltakm . d(-1)) attenuated the effect of the less active twins' BMIs on their active MZ twins' BMI (females: -14.3% per Deltakm . d(-1), P < 10(-7); males: -7.4% per Deltakm . d(-1), P = 0.004), such that by 4 Deltakm . d(-1), the inherited risk was reduced by 58.8% in females and 29.6% in males. CONCLUSIONS: These results are consistent with the attenuation of the inherited risk of excess body weight by running, which is remarkable because BMI regulation is assumed to be multifactorial, its genetic inheritance is polygenic, and no single genetic polymorphism currently explains >1% of the BMI variance.
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