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Immune-Developmental Processes Contribute to Schizophrenia Risk: Insights From a Genetic Overlap Study With Height
Cato Romero1, Christiaan de Leeuw2, Marijn Schipper2
1Department of Child and Adolescent Psychiatry and Psychology, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Biological Psychiatry
|March 12, 2025
Summary
Shorter stature is genetically linked to schizophrenia (SCZ) risk, involving pituitary and immune cells. This study used genetic data to explore the SCZ-height relationship, identifying key genes and biological pathways.
Area of Science:
- Genetics
- Psychiatry
- Human Biology
Background:
- Shorter stature is phenotypically associated with an increased prevalence of schizophrenia (SCZ).
- The underlying genetic basis for this observed association remains unclear.
Purpose of the Study:
- To investigate the genetic relationship between schizophrenia and height.
- To identify shared genetic factors and biological pathways influencing both traits.
Main Methods:
- Utilized genome-wide genetic data from over 513,000 participants.
- Applied advanced genetic methods including gene set, tissue, and cell type analyses.
- Conducted local genetic correlation, conditional analyses, and fine-mapping of effector genes.
Main Results:
- Identified 142 genes associated with both SCZ and height, enriched in 3 functional gene sets.
- Implicated the pituitary and mesenchymal stem cells for height, and thyrotropic cells for SCZ.
- Found significant local genetic correlations in 9 genomic regions, including the MHC region, with shared signals linked to white blood cell count.
Conclusions:
- Thyrotropic cells and immune response sensitivity during height development contribute to schizophrenia risk.
- Highlights shared genetic underpinnings between physical stature and psychiatric disorders.
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