Abstract PL01-03: Racial/ethnic differences in the genetics of obesity.

The prevalence of obesity has been increasing on a global scale over the past few decades. Obesity has been associated with cancer risk and many chronic diseases, directly affecting health outcomes and reducing overall quality of life. The understanding of population differences in obesity-related measurements and outcomes, particularly those observed among racial/ethnic groups, is of great interest to the science and public health communities. It is generally accepted that the accumulation of adipose tissue is responsive to a disruption in energy balance; however, the specific factors influencing the disruption of energy balance are not completely understood. Social, dietary and physical activity factors have all been considered as possible causes for perturbations in adipose tissue accretion, and thereby the obesity epidemic. Although all of these factors seem to influence obesity outcomes to varying degrees, research has demonstrated that racial/ethnic differences in obesity encompass more than just descriptive information. When individuals from different racial/ethnic groups are exposed to experimentally controlled weight-loss interventions, differences in body composition and physiological parameters emerge among and between groups. The reasons underlying these observed differences in response are not clear; however, they appear to be influenced by two primary aspects. First, “race/ethnicity” is a complex social construct that carries historical and individual identity, and correlates with biological factors. Second, it is difficult to independently and synergistically assess the contributions of genetic, behavioral, and environmental factors known to influence population differences in complex traits. A racial/ethnic “deconstruction” approach has emerged to disentangle the etiology of racial/ethnic differences in adipose tissue acquisition and accumulation. This approach relies on the scientific evaluation of the social environment, behavioral practices, and ancestral genetic background as contributors to variation in adiposity among individuals of diverse backgrounds. Previous scientific studies have demonstrated that differences in body composition parameters among multiethnic samples from the United States are not due to dietary, exercise, or socio-environmental factors alone, but rather are due to their ancestral genetic background, supporting an undeniable role of genetics in population differences in obesity-related outcomes. In general, racial/ethnic genetic influences are documented when the relationship between a phenotype and a genotype is significant in one population, but not in another. The genetic contributions to racial/ethnic differences in obesity and body composition parameters have been further qualified by genome-wide association analyses and candidate gene approaches, showing that genes which impact obesity-related traits in one population may not necessarily exert the same influence in another population. Genetic association studies in diverse populations include the statistical adjustment of ancestral background through estimates of genetic admixture, which are incorporated as a covariate in statistical testing, controlling for population stratification and reducing Type I and Type II error rate. The search toward the understanding of nature and nurture in obesity continues to be a challenge. The most noteworthy reason for this centers on the complexity of obesity itself: a multifaceted trait whereupon many genetic and environmental influences act and interact to create an outcome that represents the end of a cumulative process. Scientific research is beginning to explore approaches where the multifactorial nature of obesity is considered in experimental designs, such as the inclusion of individual's genetic ancestral background, socioeconomic status, cultural factors and behavioral practices. These approaches are believed to provide better insights into the etiology of obesity as an epidemiological risk, and give hope for the development of intervention strategies to address the obesity epidemic. Citation Format: Jose R. Fernandez. Racial/ethnic differences in the genetics of obesity. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PL01-03.