| Title: | BMI-driven multi-omics analysis profiles the molecular mechanism of psycho-metabolic nexus and contributes to risk stratification |
| Journal: | Communications Biology |
| Published: | 24 Jul 2026 |
| DOI: | https://doi.org/10.1038/s42003-026-10724-9 |
| URL: | https://www.nature.com/articles/s42003-026-10724-9_reference.pdf |
Publication 21366
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Obesity and psychiatric disorders frequently co-occur, yet the heterogeneous genetic mechanisms underlying this comorbidity remain elusive. Here, we stratify the polygenic architecture of body mass index (BMI) into five biologically distinct clusters based on metabolic signatures and construct partitioned polygenic scores (pPGSs) for each. Using individual-level data from the UK Biobank (N = 310,708), we identify cluster-specific psychiatric risk profiles, with amino acid-related clusters showing the strongest associations. These effects are markedly modulated by sex and BMI: underweight individuals and females show amplified psychiatric vulnerability, while obesity attenuates certain associations. Integration of proteomic and metabolomic data reveals key molecular mediators, including TNN, LEP, and ANGPT2, that influence psychiatric outcomes in a BMI- and sex-dependent manner. Mediation analyses demonstrate that pPGSs primarily exert indirect effects on psychiatric disorders through immune and metabolic molecular networks. These findings highlight the functional heterogeneity of BMI genetics, providing a framework for precision psychiatry.</p>
11 Authors
- Xiaonan Guo
- Yu Feng
- Peng Huang
- Ningning Jia
- Zeyu Qin
- Lingzhuo Kong
- Yiqing Chen
- Shuxiang Yang
- Jiayi Zhang
- Sheng Yang
- Shaohua Hu
1 Application
| Application ID | Title |
|---|---|
| 144904 | Integrative Deep Learning Analysis of UKBB Data: Bridging Genotypes, Medical Imaging, and Polygenic Scores for Precision Health Insights |
Enabling scientific discoveries that improve human health