| Title: | Immune-Developmental Processes Contribute to Schizophrenia Risk: Insights From a Genetic Overlap Study With Height |
| Journal: | Biological Psychiatry |
| Published: | 10 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40073922/ |
| DOI: | https://doi.org/10.1016/j.biopsych.2025.02.902 |
Publication 16612
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Abstract
BACKGROUND: Shorter stature has been phenotypically linked to increased prevalence of schizophrenia (SCZ), but the nature of this association is unknown.</p>
METHODS: Using genome-wide genetic data from 513,398 participants, we studied the SCZ-height relationship on a genetic level. Applying novel genetic methods and tools, we analyzed gene sets, tissue types, cell types, local genetic correlation, conditional genetic analyses, and fine-mapping of effector genes to scrutinize the SCZ-height relationship.</p>
RESULTS: We identified 142 genes statistically associated with both SCZ and height and found enrichment in 3 functional gene sets. Genetic annotations implicated the pituitary and specifically mesenchymal stem cells for height and thyrotropic cells for SCZ. While the global SCZ-height genetic correlation was nonsignificant, 9 genomic regions showed robust local genetic correlations (7 negative, 6 in the major histocompatibility complex [MHC] region). The shared genetic signal for SCZ and height within the 6 MHC regions was partially explained by mutual genetic overlap with white blood cell count, particularly lymphocytes. Fine-mapping prioritized 3 shared effector genes (GIGYF2, HLA-C, and LIN28B) involved in immune response sensitivity and the development of immune and pituitary cell types.</p>
CONCLUSIONS: Overall, our findings suggest an involvement during height development of thyrotropic cells and immune response sensitivity that contribute toward the risk of SCZ.</p>
9 Keywords
- Adult
- Body Height
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Major Histocompatibility Complex
- Male
- Schizophrenia
10 Authors
- Cato Romero
- Christiaan de Leeuw
- Marijn Schipper
- Bernardo de A P C Maciel
- Martijn P van den Heuvel
- Rachel M Brouwer
- August B Smit
- Frank Koopmans
- Danielle Posthuma
- Sophie van der Sluis
1 Application
| Application ID | Title |
|---|---|
| 16406 | Causes of individual differences in cognitive and mental health |
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