Related Experiment Video
Updated: Jul 1, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Schizophrenia Genetic Liability Drives Chronic Disease Risk in Unaffected Individuals through Immune and Metabolic
Wenming Wei1,2, Bolun Cheng1,2, Dan He1,2
1NHC Key Laboratory of Environment and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Introduction:
Comorbidity between schizophrenia (SCZ) and chronic diseases is well documented. However, it remains unknown whether unaffected individuals with elevated SCZ genetic liability also face increased risk, and what biological pathways may underlie these associations.
Methods:
We analyzed 426,237 UK Biobank participants without SCZ to test associations between SCZ polygenic risk score (SCZ-PRS) and 24 chronic diseases using logistic regression. Multi-omics mediation analysis incorporated seven inflammatory markers, 1,463 plasma proteins, and 250 circulating metabolites to delineate intermediate pathways linking genetic liability to disease outcomes. Genetic colocalization analyses were further conducted to determine whether SCZ genetic liability and chronic diseases share common association signals at the locus level.
Results:
Higher SCZ-PRS was associated with increased risk of asthma (odds ratio [OR] = 1.018, 95% confidence interval [CI]: 1.008-1.029), chronic obstructive pulmonary disease (1.033, 1.017-1.050), liver disease (1.033, 1.015-1.051), peptic ulcer (1.032, 1.013-1.051), and fluid/electrolyte disorders (1.027, 1.014-1.040), while conferring reduced risk of diabetes (0.979, 0.968-0.991) and renal disease (0.978, 0.964-0.992). Multi-omics mediation revealed that these bidirectional associations were linked to immune cell activity (notably eosinophils, neutrophils, and monocytes), lipid and energy metabolism (lipoprotein composition, fatty-acid unsaturation, creatinine, lactate), and immune-regulatory proteins (e.g., HLA-E, CD1C, SPINT1). Shared genetic signals, notably at HLA and SLC39A8, reinforced these immune-metabolic pathways.
Conclusions:
SCZ-PRS is associated with multiple chronic diseases among unaffected individuals, and these associations suggest shared biological pathways. These findings support a psycho-neuro-immune-metabolic interpretation of SCZ-related chronic physical comorbidity and a more integrated psychosomatic understanding of the shared biology linking psychiatric vulnerability with chronic physical disease.
More Related Videos
09:37A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
09:09Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
Related Concept Videos
Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin studies.
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within the...
Psychological and Sociocultural Causes of Schizophrenia
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Autoimmune Disorders
Concept and Mechanism of Autoimmune Diseases
The immune system...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu