Some genes show consistent effects, while others show significant ancestral heterogeneity
By Elana Gotkine HealthDay Reporter
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.
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.
The researchers identified 13 genes in a cross-ancestry meta-analysis, including YLPM1, RIF1, GlGYF1, SLC5A3, and GRM7, 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, MC4R, and SLTM; significant ancestral heterogeneity was seen for GRM7 and APBA1. Obesity penetrance increased additively with polygenic risk; additional associations were seen in phenome-wide studies including YLPM1 with altered mental status. Cardiometabolic comorbidities were also influenced by these genes, including GlGYF1 and SLTM toward type 2 diabetes, with or without BMI as a mediator, and altered levels of plasma proteins including LECT2 and NCAN, which affect BMI.
“The novel genes identified in our study highlight both established and emerging pathways in obesity biology,” Banerjee said in a statement. “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.”
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