ArticleEBioMedicine2025
Shared genetic architecture and bidirectional clinical risks within the psycho-metabolic nexus.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Genetic interconnections between personality-related phenotypes and psychiatric disorders.European archives of psychiatry and clinical neuroscience · 2026Article
- Cross-trait genetic analysis maps shared polygenic architecture between primary aldosteronism and blood pressure to adrenal cell states.Journal of translational medicine · 2026Article
- Plasma Metabolomic and Proteomic Profiling of the Mechanisms Underlying the Cumulative Impact of Co-occurring Psychiatric Disorders on Atopic Dermatitis.Acta dermato-venereologica · 2026Article
- Cross-ancestry genetic architecture reveals shared biological pathways of major psychiatric disorders.Molecular psychiatry · 2026Article
- Genetic and sociodemographic factors associated with trajectories of physical and mental health multimorbidity in a South Asian cohort in the UK: A multistate modelling analysis.PLoS medicine · 2026Article
- Cross-ancestry pleiotropic analysis of imaging-derived phenotypes enhances risk stratification of depression.Molecular psychiatry · 2026Article
- Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation.medRxiv : the preprint server for health sciences · 2026Article
- Micro-and Nano-Plastic Exposure as an Emerging Risk for Atherosclerotic Cardiovascular Disease.Current atherosclerosis reports · 2026Review
- Depression in Autism Spectrum Disorder: Neurobiological Convergence and Emerging Therapeutic Strategies.Biology · 2026Review
- Profiling the Onco-metabolic Nexus and Improving Cancer Risk Prediction Performance: A Large-scale Cohort and Genome-Wide Pleiotropic Analysis.Cancer research communications · 2026Article
- Article
- Shared Genetic Liability across Systems of Psychiatric and Physical Illness.Nature communications · 2026Article
- Integrated gut microbiota and metabolome analyses link anger to metabolic dysregulation in patients with type 2 diabetes mellitus.Frontiers in microbiology · 2026Article
- Multi-omics and comprehensive multi-trait analysis identify shared genetic etiology of heart failure and related cancers.Human genomics · 2025Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Bidirectional genetic overlap between psychiatric disorders and high-density lipoprotein cholesterol levels.Lipids in health and disease · 2025Article
- Genetic underpinnings and causal effects of brain structure and function on chronic pain intensity.Nature communications · 2025Article
- PGSFusion streamlines polygenic score construction and epidemiological applications in biobank-scale cohorts.Genome medicine · 2025Article
- Integrating causal human genetics andFrontiers in molecular biosciences · 2025Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing evidence suggests a complex interplay between psychiatric disorders and metabolic dysregulations. However, most research has been limited to specific disorder pairs, leaving a significant gap in our understanding of the broader psycho-metabolic nexus.
methodsThis study leveraged large-scale cohort data and genome-wide association study (GWAS) summary statistics, covering 8 common psychiatric disorders and 43 metabolic traits. We introduced a comprehensive analytical strategy to identify shared genetic bases sequentially, from key genetic correlation regions to local pleiotropy and pleiotropic genes. Finally, we developed polygenic risk score (PRS) models to translate these findings into clinical applications.
findingsWe identified significant bidirectional clinical risks between psychiatric disorders and metabolic dysregulations among 310,848 participants from the UK Biobank. Genetic correlation analysis confirmed 104 robust trait pairs, revealing 1088 key genomic regions, including critical hotspots such as chr3: 47588462-50387742. Cross-trait meta-analysis uncovered 388 pleiotropic single nucleotide variants (SNVs) and 126 shared causal variants. Among variants, 45 novel SNVs were associated with psychiatric disorders and 75 novel SNVs were associated with metabolic traits, shedding light on new targets to unravel the mechanism of comorbidity. Notably, RBM6, a gene involved in alternative splicing and cellular stress response regulation, emerged as a key pleiotropic gene. When psychiatric and metabolic genetic information were integrated, PRS models demonstrated enhanced predictive power.
interpretationThe study highlights the intertwined genetic and clinical relationships between psychiatric disorders and metabolic dysregulations, emphasising the need for integrated approaches in diagnosis and treatment.
fundingThe National Key Research and Development Program of China (2023YFC2506200, SHH). The National Natural Science Foundation of China (82273741, SY).
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