Landmark Study Identifies 13 genes Linked to Obesity Across Diverse Ancestries
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A groundbreaking new study published October 30 in Nature Communications has identified 13 genes associated with obesity across six distinct ancestral groups,offering a more comprehensive understanding of the genetic factors driving this global health crisis. The research,conducted by scientists at Penn State and involving nearly 850,000 adults,reveals five previously unknown genetic links to obesity,potentially paving the way for more effective,personalized treatments.
addressing Ancestral Bias in Obesity Research
For years, genetic research into obesity has been hampered by a meaningful bias towards populations of european ancestry. This limitation has likely obscured the identification of genes that play a crucial role in obesity across all populations. To overcome this, the researchers combined data from the UK Biobank, encompassing over 450,000 adults primarily of European descent, and the All of Us Research Program, a U.S. National Institutes of Health initiative representing a more diverse cohort of nearly 385,000 individuals. The six continental ancestries included in the study were African, American, East Asian, European, Middle Eastern, and south Asian.
The team focused on identifying rare, “loss-of-function” variants – genetic changes that disrupt a gene’s normal function – as these are more likely to have a ample impact on disease risk. By combining data from these diverse populations, they were able to pinpoint 13 genes considerably associated with body mass index (BMI), a key indicator of obesity. eight of these genes were already known to be linked to obesity, while five – YLPM1, RIF1, GIGYF1, SLC5A3, and GRM7 – represent entirely new discoveries.
Novel Genes Show Significant Impact on Obesity Risk
These newly identified genes appear to confer a roughly three-fold increase in the risk of severe obesity, comparable to the impact of well-established obesity genes like MC4R and BSN. Like their previously known counterparts,these genes are expressed in both the brain and adipose (fat) tissue,and are linked to obesity-related traits such as increased body-fat percentage.
“YLPM1, for example, is an understudied transcription factor expressed in brain tissues, with links to mental disorders,” noted a lead researcher. “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 affect across ancestries, similar to MC4R.”
Unraveling the Link between Obesity and Comorbidities
The study also delved into how these genes influence obesity-related health problems, or comorbidities, such as Type 2 diabetes and heart disease.Using a statistical technique called mediation analysis, the researchers persistent that some genes increase the risk of these conditions both directly and indirectly, by first increasing BMI. for instance, genes like BSN, GIGYF1, and SLTM were found to elevate the risk of type 2 diabetes through both pathways, with the direct effect on disease risk being more pronounced.
Moreover, analysis of plasma proteomics data – a comprehensive list of proteins in the blood – revealed changes in circulating proteins linked to the identified obesity genes, potentially highlighting new drug targets and biomarkers for future therapies.
The Power of Cross-Ancestry Studies for Precision Medicine
The findings underscore the critical importance of conducting research that includes diverse populations. “Some of the previously discovered obesity genes appear to only have significant association to obesity in Europeans, which could limit their potential as therapeutic targets for a global population,” explained a senior official. “Our cross-ancestry approach is helping us develop a more comprehensive view of the factors involved in obesity, which will hopefully help us develop effective therapies that can be applied through precision medicine.”
This research was funded by the U.S. National Institutes of Health, with additional support from Penn state and the Penn State Huck Institutes of the Life Sciences. The study highlights Penn State’s commitment to addressing real-world health challenges and underscores the vital role of continued federal investment in scientific research.
