An international team of researchers have identified a new genetic variant linked to obesity that is unique to African populations. By studying the genomes of both West African and African-American participants, the team were able to use a genome-wide association study (GWAS) to identify the gene. The research was published today in Obesity.

The research is a result of an international collaboration between the National Human Genome Research Institute (NHGRI) and the Centre for Research on Genomics and Global Health (CRGGH) (both NIH organisations), the University of Lagos, the University of Nigeria Teaching Hospital, Kwame Nkumrah University of Science and Technology in Ghana, and the University of Ghana Medical School.

In 2014, the World Health Organisation estimated that there were more than 1.9 billion adults in the world who were overweight, roughly 600 million of whom were obese. Obesity can contribute to morbidity and premature death by increasing a person’s risk of diabetes, hypertension, heart disease, and even some forms of cancer. While obesity is generally linked to a person’s lifestyle (diet, exercise, etc.), in some cases there are strong contributions from a person’s genetic make-up.

This study uncovered genetic variants within the semaphorin-4D (SEMA4D) gene, which plays a role in cell signalling, the immune response, and bone formation. Their research showed that people with genetic differences in the gene were on average 6 pounds heavier than people without the variant.

Despite people of African descent having an increased risk of obesity, the majority of past work has focused on European participants and data. In the USA, the African-American population has the highest age-adjusted rate of obesity of all racial demographics. This new research helps to highlight the divide between research and disease occurrence, as SEMA4D is absent from both European and Asian genomes.

“We wanted to close this unacceptable gap in genomics research,” said Charles Rotimi, Ph.D., Chief of NHGRI’s Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch and Director of CRGGH.

This is the first study to use a GWAS to investigate the genomic factors of obesity in continental Africans. The team initially tested 1,570 West Africans, then repeated their work with individual cohorts of 1,411 West Africans and 9,020 African-Americans.

“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 Ayo Doumatey, Ph.D., co-lead scientist of the study and staff scientist at CRGGH. “These findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk.”

The team hope to replicate their findings in more populations and to use cells lines and models to better understand variants in the SEMA4D gene. They also want to conduct larger studies in different populations to identify other genomic factors that may be involved in the development of obesity.

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