Are genes destiny? Exploring the role of intrauterine environment in moderating genetic influences on body mass

Objectives: Genes influence every aspect of human behavior, physiology, and health. Obesity, a major global public health concern, is no exception. However, relatively little is known about whether environmental factors moderate the effects of genetic influences on body mass. By incorporating molecular genetics and the fetal origins of obesity hypothesis into a gene-environment interaction framework, this study investigates how the effect of the obesity-associated gene (FTO) interacts with the effect of intrauterine environment to influence body mass during adulthood. Methods: This study uses data from the Wisconsin Longitudinal Study, and uses sibling comparisons that allow for quasi-experimental variation in both genetic and environmental factors. Results: This study found positive, but noisy, within-family estimates of the FTO-body mass index (BMI) association. The association between birth weight and adult BMI was robust to controlling for unobserved family background factors. More importantly, this study revealed that the association between having a risk allele of the FTO gene and BMI (and obesity status) is largely concentrated among individuals who were heavier at birth. This provides evidence of a gene-environment interaction on BMI (and the development of obesity). Conclusions: Genes are not destiny and environmental factors may offset the effects of obesity-promoting genes. Public health efforts to counteract genetic effects on body mass may begin as early as in utero. Efforts to prevent higher birth weight may thus help reduce the risk of obesity later in life, by directly addressing the programming effects of the in utero environment and also indirectly moderating obesity-promoting genetic effects.