On January 15, 2026, the research team led by Professor Weng Jianping (President of Anhui Medical University, Chair Professor at University of Science and Technology of China) and Researcher Zheng Xueying published a study in Metabolism entitled “Integrative Functional Genomics and Fine-Mapping Identify Regulatory Mechanisms of Multivariate Obesity GWAS and Its Cardiometabolic Implications”.By constructing an integrative analytical framework for multi-trait and multi-omics data, the study systematically revealed the genetic mechanism of the neuro-adipose regulatory axis underlying obesity, providing a novel genetic basis for precision metabolic intervention.Ph.D. candidates Wang Suijian and Liu Sihua from Anhui Medical University are co-first authors of the paper.
Obesity is not a single trait but a systemic disease co-regulated by the central nervous system and adipose tissue, with a highly complex genetic basis that has long been difficult to fully dissect by traditional single-trait genome-wide association studies (GWAS).Most existing studies use body mass index (BMI) as the obesity phenotype, which cannot distinguish fat distribution patterns critical for metabolic and cardiovascular risk, such as visceral fat and hepatic fat, limiting the discovery of genetic mechanisms and precise intervention targets for obesity.
The results showed that multivariate analysis identified a total of 548 obesity-associated genetic loci, including 45 novel signals undetected by conventional single-trait GWAS, significantly improving the power of genetic discovery.By further integrating chromatin accessibility in adipose tissue, enhancer–promoter interactions, eQTL data, and transcriptome-wide and proteome-wide association studies (TWAS/PWAS), the team systematically dissected the potential regulatory target genes from non-coding variants.
Through fine-mapping and integration of multi-omics evidence, the study finally prioritized 150 high-confidence candidate genes.Functional enrichment analysis revealed that these genes are not only involved in lipid metabolism and transcriptional regulation but are also significantly enriched in pathways related to neurotransmission, synaptic structure, and neural development, indicating a key regulatory role of the central nervous system in the pathogenesis of obesity.MAGMA analysis further demonstrated that these genes are significantly enriched in brain regions including the cerebellum, hippocampus, hypothalamus, and nucleus accumbens, pointing to a cross-tissue neuro-metabolic regulatory network.
By integrating seven independent lines of evidence, including fine-mapping, transcriptomics, proteomics, single-cell expression, and genetic colocalization, the study ultimately identified a set of highly consistent core regulatory genes, including MED13L, GBE1, CADM2, PIK3R3, ERBB4, PTK2B, and TCF7L2.These genes exhibit highly consistent genetic regulatory signals in both adipose and brain tissues, forming a potential “neuro-adipose regulatory hub”.