Genetic Variant Linked to Obesity in Africans, African Americans

A variant of SEMA4D may be why there is a high prevalence of obesity among individuals of African ancestry.

A new study links a genomic variant primarily found in Africans and African Americans to an increased risk of obesity. The variant is carried by 1% of West Africans, African Americans, and others of African descent, and may explain why obesity is common in certain families, according to a study published by Obesity.

In the study, the authors found that those with a semaphorin-4D (SEMA4D) variant were approximately 6 pounds heavier than those without the variant. This gene is involved with cell signaling, immune response, and bone formation, according to the study. Previous research has focused on individuals of European descent, even though there is an increased risk of obesity among individuals of African descent.

Obesity affects many individuals worldwide, and increases the risk of developing diabetes, hypertension, heart disease, and cancer. These factors lead to an increased risk of premature death and increased healthcare spending. Although obesity can be brought on by excessive eating and sedentary behaviors, it is also known to have a genetic component.

However, not all ethnic groups have the same risk of developing obesity. African Americans have the highest age-adjusted rates of obesity. Understanding what drives this increased risk may lead to individualized treatments or prevention approaches.

This is the first research to use a genome-wide association study to examine the genomic basis of obesity in continental Africans, according to the study. In the study, the investigators compared genomes of individuals who were and were not obese to determine genetic variants linked to obesity.

A majority of previous studies have only looked at individuals of European descent who do not have the SEMA4D variant.

“We wanted to close this unacceptable gap in genomics research,” said Charles N. Rotimi, PhD, chief of National Human Genome Research Insitute’s Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch and director of the Center for Research on Genomics and Global Health at National Institutes of Health.

Through examining the genome of individuals of African descent, the authors were able to determine that the SEMA4D variant may cause an increase in obesity among this population, while not affecting others.

“By studying people of West Africa, the ancestral home of most African-Americans, and replicating our results in a large group of African-Americans, we are providing new insights into biological pathways for obesity that have not been previously explored,” said co-lead researcher Ayo P. Doumatey, PhD. “These findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk.”

The authors plan to continue their research in additional populations, and conduct novel studies in cell lines and zebrafish with the goal of identifying how variants in SEMA4D play a role in obesity.

Newer studies show that the SEMA4D genetic variant overlaps a region of DNA called an “enhancer,” which can increase the work of a gene. To further determine the role of the variant, the authors plan to conduct larger studies of DNA sequencing indifferent populations. They hope to discover other genetic factors that influence diabetes risk, according to the study.

“Eventually, we hope to learn how to better prevent or treat obesity,” Dr Rotimi concluded.