Behavioral and Environmental Modification of the Genetic Influence on Body Mass Index: A Twin Study

Abstract

Body mass index (BMI) has a strong genetic basis, with a heritability around 0.75, but is also influenced by numerous behavioral and environmental factors. Aspects of the built environment (e.g., environmental walkability) are hypothesized to influence obesity by directly affecting BMI, by facilitating or inhibiting behaviors such as physical activity that are related to BMI, or by suppressing genetic tendencies toward higher BMI. The present study investigated relative influences of physical activity and walkability on variance in BMI using 5079 same-sex adult twin pairs (70 % monozygotic, 65 % female). High activity and walkability levels independently suppressed genetic variance in BMI. Estimating their effects simultaneously, however, suggested that the walkability effect was mediated by activity. The suppressive effect of activity on variance in BMI was present even with a tendency for low-BMI individuals to select into environments that require higher activity levels. Overall, our results point to community- or macro-level interventions that facilitate individual-level behaviors as a plausible approach to addressing the obesity epidemic among US adults.

Figure 1

Path diagram of gene-by-environment interaction in the presence of a gene-environment correlation, with moderation of variance in body mass index (BMI). The paths representing the ACE covariances between the moderator (walkability or MVPA) and BMI vary as a function of the moderator; these regression paths test Hypotheses 1a and 1b. Au, Cu, and Eu are the residual variance components of BMI (i.e., the variance in BMI that remains after accounting for variance shared with the moderating variable), and are functions of the moderator and covariates age, and gender; these paths test Hypotheses 2a and 2b. Only one twin is shown for clarity; the A and C components of the moderator and BMI correlate across twins (r_A = 1.0 for monozygotic twins, 0.5 for dizygotic twins; r_C = 1.0 for all pair types); the E components are not correlated across twins. Individual-level covariates income and education were allowed to correlate across twins.

Figure 2

Path diagram of G×E interaction in the presence of rGE, with moderation of variance in BMI by both environmental walkability and moderate-to-vigorous physical activity (MVPA). This model is an extension of the model illustrated in Figure 1. The residual variances Au, Cu, and Eu vary as a function of walkability, MVPA, and covariates age, and gender; these paths test Hypothesis 3. Only one twin is shown for clarity; the A and C components of the phenotypes correlate across twins (r_A = 1.0 for monozygotic twins, 0.5 for dizygotic twins; r_C = 1.0 for all pair types); the E components are not correlated across twins. Individual-level covariates income and education correlated across twins.

Figure 3

Regression of BMI on environmental walkability (top left panel) and physical activity (bottom left panel) and 95% confidence intervals (shaded areas). Right panels show the same relations, but represented as genetic and nonshared environmental correlations. The asterisks (*) indicate that the magnitude of the regression (or correlation) of BMI on MVPA (or walkability)

Figure 4

Illustrative analysis of the main effects of walkability (a) and MVPA (b) on BMI. Figure 4a shows pair differences in BMI as a function of pair differences in walkability in the population (referred to as the “phenotypic difference”) and within pairs of MZ twins (referred to as the “MZ difference”). Figure 4b shows BMI at lower (0-2 hours per week; left panel) and higher (4-6 hours per week; right panel) levels of MVPA; within each panel, the twin engaging in less physical activity (dark gray) is compared with the twin engaging in more physical activity (light gray) in MZ and DZ twin pairs.

Figure 5

Gene by environment interaction between body mass index and walkability (left panel) and moderate-to-vigorous physical activity (right panel). The stacked variances illustrate how the total variance in BMI decreases as a function of walkability and MVPA. White dotted lines represent the 95% confidence intervals of each variance component of BMI as a function of walkability and MVPA.

Figure 6

Absolute pair difference in body mass index as a function of the pair average environmental walkability (left panel) and pair average moderate to vigorous physical activity (right panel). Shaded region represents the 95% confidence interval around the smoothed loess curves fit to the data. The area between the MZ and DZ loess curves represents the additive genetic variance in BMI.