Obesity is a global health problem, contributing to premature death and morbidity by increasing a person's risk of developing diabetes, hypertension, heart disease and some cancers. While obesity mostly results from lifestyle and cultural factors, including excess calorie intake and inadequate levels of physical activity, it has a strong genomic component. The burden of obesity is, however, not the same across U.S. ethnic groups, with African-Americans having the highest age-adjusted rates of obesity. Interestingly, most of the genomic studies conducted on obesity to date have been in people of European ancestry, despite an increased risk of obesity in people of African ancestry.
According to an article published online the journal Obesity (13 March 2017), an international team of researchers has conducted the first study of its kind to look at the genomic underpinnings of obesity in continental Africans and African-Americans. The study discovered that approximately 1% of West Africans, African-Americans and others of African ancestry carry a genomic variant that increases their risk of obesity, a finding that provides insight into why obesity clusters in families. Results from the study showed that people with genomic differences in the semaphorin-4D (SEMA4D) gene were about six pounds heavier than those without the genomic variant.
This is the first study to use a Genome-Wide Association Study (GWAS) to investigate the genomic basis of obesity in continental Africans. A GWAS compares the genomes of people with and without a health condition - in this case, people who are obese and those who are not -- to search for regions of the genome that contain genomic variants associated with the condition. Most previous studies on obesity using a GWAS have been conducted with populations of European ancestry; these studies wouldn't have found the SEMA4D genomic variant, which is absent in both Europeans and Asians.
According to the authors, by studying people of West Africa, the ancestral home of most African-Americans, and replicating our results in a large group of African-Americans, new insights are now available into biological pathways for obesity that have not been previously explored. The authors added that these findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk.
The authors plan to replicate these findings in more populations and conduct experiments using cell lines and model organisms such as zebrafish to identify the role of genomic variants in SEMA4D in obesity and obesity-related traits. (The SEMA4D gene plays a role in cell signaling, the immune response and bone formation.) Available data show that the newly identified genomic variant overlaps a region of DNA called an enhancer that can be activated to increase the work of a particular gene. The authors plan to conduct larger studies of DNA sequencing of this gene in different human populations with the hope of identifying other genomic factors that may be associated with obesity. The overall goal of the program is to learn how to better prevent or treat obesity.