Millions of people around the world are considered obese, a condition that is associated with a range of other life-threatening disorders including type 2 diabetes and cardiovascular disease. Although some lifestyle choices and habits are related to the development of obesity, there are also genes, and variations in gene sequences that have been connected to the risk of obesity. Now, scientists have conducted a large analysis of genetic and health data across various ancestry groups, and with this data, revealed new genes linked to the risk of obesity. The findings have been reported in Nature Communications.
This study took into account data from about 850,000 adults from six continental ancestries: African, American, East Asian, European, Middle Eastern, and South Asian, to identify thirteen novel obesity-associated genes. This data came from the UK Biobank and the All of Us Research Program by the US National Institutes of Health, and this diversity helped the researchers to identify novel genes. While eight of these genes have been associated with obesity in previous work, such as MC4R and BSN; five are newly identified by this study: GIGYF1, GRM7, RIF1, SLC5A3 and YLPM1. Variations in these genes can lead to as much as a three-fold increase in a carrier’s risk of obesity.
Previous work on obesity risk genes has primarily focused on people with European ancestry. "Obesity touches millions, but most studies have focused on a few," said first study author Deepro Banerjee, a graduate student at Pennsylvania State University.
"The novel genes identified in our study highlight both established and emerging pathways in obesity biology. YLPM1, for example, is an understudied transcription factor expressed in brain tissues, with links to mental disorders. It's a clear example of a gene whose lower prevalence in one population may have obscured it historically. In our cross-ancestry analysis, YLPM1 shows a remarkably consistent effect across ancestries, similar to MC4R," Banerjee said.
"Studies in a single population can lead us to miss important genes that are shared across populations but may not rise to statistical significance in any one of them, even if they are clinically important in that population. New databases that include more representation of individuals with ancestries from around the world are helping to alleviate this bias, but we still need more data from non-European populations,” added study co-author Professor Santhosh Girirajan, head of the Department of Biochemistry and Molecular Biology at Penn State.
Some of the genes identified in this study are also related to other disorders like type 2 diabetes and heart disease, which can help explain why obese individuals are at risk for other diseases.
Sources: Pennsylvania State University, Nature Communications
