Study identifies African-specific genomic variant associated with obesity
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. They discovered that approximately 1 percent 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. Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and their African collaborators published their findings March 13, 2017, in the journal Obesity.
People with genomic differences in the semaphorin-4D (SEMA4D) gene were about six pounds heavier than those without the genomic variant, according to the study. 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.
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, said Charles N. Rotimi, Ph.D., chief of NHGRI's Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch and director of the Center for Research on Genomics and Global Health (CRGGH) at NIH. CRGGH examines the socio-cultural and genomic factors at work in health disparities – the negative health outcomes that impact certain groups of people – so they can be translated into policies that reduce or eliminate healthcare inequalities in the United States and globally.
This is the first study to use a Genome-Wide Association Study (GWAS) to investigate the genomic basis of obesity in continental Africans, said Guanjie Chen, M.D., study co-lead and a CRGGH staff scientist. 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.
"We wanted to close this unacceptable gap in genomics research," Dr. Rotimi said.
"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 P. Doumatey, Ph.D., study co-lead and CRGGH staff scientist. "These findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk."
Dr. Rotimi and his colleagues 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, he said. They 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.
"Eventually, we hope to learn how to better prevent or treat obesity," Dr. Rotimi said.
Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH — Charles N. Rotimi, Adebowale A. Adeyemo, Amy R. Bentley, Guanjie Chen, Ayo P. Doumatey, Lin Lei, Daniel Shriner, Jie Zhou
College of Medicine, University of Lagos, Endocrine and Metabolic Unit, Lagos, Nigeria — Olufemi Fasanmade, Thomas Johnson
University of Nigeria Teaching Hospital, Department of Hematology, Enugu, Nigeria — Godfrey Okafor, Johnnie Oli
Kwame Nkumrah University of Science and Technology, School of Medical Sciences, Kumasi, Ghana — Benjamin Eghan Jr., Kofi Agyenim-Boateng, Joseph Acheampong
University of Ghana Medical School, Department of Medicine and Therapeutics, Accra, Ghana — Albert Amoah
University of Maryland School of Medicine, Baltimore, Maryland — Clement Adebamowo
CRGGH is administered by NHGRI and supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the NIH Office of the Director. For more information, visit: https://crggh.nih.gov/
National Human Genome Research Institute (NHGRI) is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at: http://www.genome.gov.
National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical and translational medical research, and is investigating the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.