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Publications

Journal Article Epublish

PubMed: 40703095 DOI: 10.1016/j.csbj.2025.07.029

The hidden genetic and microbial networks connecting neuropsychiatric and digestive disorders.

Comput Struct Biotechnol J 27:3114-3126

Authors: Jiayi Xiong, Tiantian Xu, Zheng Wang, Yuanfeng Huang, Shiyu Zhang, Guang Yang, Jiaqi Yang, Shuo Gao, Tianyang Wang, Xingxing Jian, Guihu Zhao, Jinchen Li, Bin Li

Affiliations

  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Centre for Medical Genetics & Hunan Key Laboratory, School of Life Sciences, Central South University, Changsha, Hunan 410008, China. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Bioinformatics Centre, Furong Laboratory, Changsha, Hunan 410008, China.
  • Bioinformatics Centre, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Centre for Medical Genetics & Hunan Key Laboratory, School of Life Sciences, Central South University, Changsha, Hunan 410008, China. Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410078, China.

Abstract

The gut-brain axis is a key interface between neuropsychiatric and digestive disorders, however, the underlying shared genetic mechanisms and microbial mediators remain poorly understood. Utilizing genome-wide association study (GWAS) data from 18 neuropsychiatric and 24 digestive disorders, along with microbial quantitative trait loci (mbQTL) data encompassing 211 taxa (N = 18,340), we conducted a comprehensive analysis integrating linkage disequilibrium score regression, MAGMA gene-based pleiotropy mapping, and Mendelian randomization. We identified 12 significant genetic correlations between gut-brain disorder pairs, including attention-deficit/hyperactivity disorder (ADHD) and fatty liver disease. In total, 5339 pleiotropic genes were discovered, with MSH5 appearing in 28 disorder pairs. Pathway enrichment analysis implicated immune regulation and synaptic signaling as core biological processes. Novel causal relationships were also uncovered, such as ADHD increasing the risk of irritable bowel syndrome. Co-localization analysis validated three causal associations. Microbiota-focused analyses further demonstrated a protective role of Actinobacteria against stroke, resolving previous inconsistencies in the literature. Collectively, these findings highlight the dual role of the gut microbiota-as both modulator and contributor-and provide critical genetic insights that may guide the development of targeted interventions across the gut-brain axis.

MeSH

Genes, Brain, Attention Deficit Disorder With Hyperactivity