Genetic Variations in PRODH and Their Impact on Schizophrenia Risk
Author Information
Author(s): Kempf Lucas, Nicodemus Kristin K., Kolachana Bhaskar, Vakkalanka Radhakrishna, Verchinski Beth A., Egan Michael F., Straub Richard E., Mattay Venkata A., Callicott Joseph H., Weinberger Daniel R., Meyer-Lindenberg Andreas
Primary Institution: National Institute of Mental Health, Department of Health and Human Services, National Institutes of Health, Bethesda, Maryland, United States of America
Hypothesis
Functional polymorphisms in PRODH are associated with schizophrenia risk and protective effects.
Conclusion
The study found that specific genetic variations in PRODH influence the risk and protection for schizophrenia through their effects on brain structure and function.
Supporting Evidence
- Functional variants in PRODH were associated with schizophrenia risk.
- The risk haplotype was linked to decreased striatal volume.
- The protective haplotype was associated with increased frontal lobe volume.
- Imaging showed altered connectivity in brain circuits related to working memory.
- Unrelated controls were used to validate the imaging findings.
- Sibling analysis indicated protective alleles were overtransmitted to unaffected siblings.
- Genetic variations in PRODH modulate enzymatic activity linked to schizophrenia.
- Findings suggest new targets for therapeutic interventions in schizophrenia.
Takeaway
Some genes can make you more likely to get sick, while others can help protect you. This study looked at a gene related to schizophrenia and found how it affects the brain.
Methodology
The study used a family-based sample and multimodal imaging genetics approach to analyze the effects of PRODH polymorphisms on schizophrenia.
Potential Biases
Potential confounding factors from population stratification were minimized by selecting a homogeneous sample.
Limitations
The study focused only on individuals of European ancestry, which may limit the generalizability of the findings.
Participant Demographics
303 probands with schizophrenia spectrum disorders, their unaffected siblings, their parents, and 370 controls, all of European ancestry.
Statistical Information
P-Value
p=0.009
Confidence Interval
95% C.I. 1.17–2.90
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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