Mutation Linked to Obesity Identified in Genome Study

Results obtained during what was probably the first genome-wide association study (GWAS) for body mass index (BMI) to be conducted in continental Africa identified a gene, carried by about 1% of West Africans, linked to hereditary obesity.

An international team of investigators from the [U.S.] National Human Genome Research Institute together with a group of African collaborators performed the GWAS for BMI on a study cohort comprising 1,570 West Africans.


The investigators identified a mutation in the Semaphorin-4D (SEMA4D) gene that was carried by approximately 1% of the test population. The SEMA4D gene plays a role in cell signaling, immune response, and bone formation. Carriers of the mutation were found to be about six pounds heavier than those without the genomic variant. Furthermore, obese individuals had higher serum SEMA4D levels as compared to normal individuals, and elevated levels of serum SEMA4D were associated with increased obesity risk.

Most previous GWAS studies on obesity have been conducted with populations of European ancestry. These studies would not have found the SEMA4D genomic variant, which is absent in both Europeans and Asians.

"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 first author Dr. Ayo P. Doumatey, a researcher with the Center for Research on Genomics and Global Health at the [U.S.] National Institutes of Health. "These findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk."

The study was published in the March 13, 2017, online edition of the journal Obesity.