Some genes show consistent effects, while others show significant ancestral heterogeneity<\/p>\n<\/h3>\n
By Elana Gotkine HealthDay Reporter<\/b>
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THURSDAY, Nov. 13, 2025 (HealthDay News) — Novel genes have been identified that confer an increased risk for obesity and are linked to obesity traits, according to a study published online Oct. 30 in Nature Communications<\/em>.<\/p>\n Deepro Banerjee and Santhosh Girirajan, M.B.B.S., Ph.D., from the Huck Institutes of the Life Sciences in University Park, Pennsylvania, conducted a gene-based rare variant association study of body mass index (BMI) involving 839,110 individuals from six ancestries across two population-scale biobanks.<\/p>\n The researchers identified 13 genes in a cross-ancestry meta-analysis, including YLPM1<\/em>, RIF1<\/em>, GlGYF1<\/em>, SLC5A3<\/em>, and GRM7,<\/em> which are expressed in the brain and adipose tissue and confer about a threefold higher risk for severe obesity; these genes are linked to obesity traits including body-fat percentage. Consistent effects were seen for YLPM1<\/em>, MC4R<\/em>, and SLTM<\/em>; significant ancestral heterogeneity was seen for GRM7<\/em> and APBA1<\/em>. Obesity penetrance increased additively with polygenic risk; additional associations were seen in phenome-wide studies including YLPM1<\/em> with altered mental status. Cardiometabolic comorbidities were also influenced by these genes, including GlGYF1<\/em> and SLTM<\/em> toward type 2 diabetes, with or without BMI as a mediator, and altered levels of plasma proteins including LECT2 and NCAN, which affect BMI.<\/p>\n “The novel genes identified in our study highlight both established and emerging pathways in obesity biology,” Banerjee said in a statement. “YLPM1<\/em>, 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.”<\/p>\n