presentation

1. Evaluation of HLA polymorphisms
in relation to schizophrenia risk and
infectious exposure
Bamne et al, Schizophr Bull (2012)
38(6): 1149-1154 September 10, 2012
doi:10.1093/schbul/sbs087
Funds: NIMH, Stanley Medical Research Institute

2. HLA variants in schizophrenia: older studies

3. HLA variants and schizophrenia: GWAS

4. Motivation for current study
Caveats Rationale
Pathogenic basis uncertain Exposure to infectious
factors?
Modest odds ratios ~ 1.2-1.8 Gene-environment
interactions?
Associations in Caucasian
ancestry samples African-Americans (trans-
ethnic mapping)

5. PAARTNERS schizophrenia study of
African-Americans
• Largest genetic study, eight US collaborative sites.
• Diagnostic evaluations, DNA, serum for all participants
• Cases: schizophrenia / schizoaffective disorder (N = 604)
• Screened adult controls from each site (N = 404)
• SNPs: iplex assays
• GWAS (N=16)
• Ancestry Informative Markers (N=22)
• Exposure using specific, sensitive antibody titers
• Herpes Simplex virus, type 1 (HSV-1),
• Cytomegalovirus (CMV),
• Toxoplasma Gondii (TOX)

6. GWAS SNPs analyzed

7. Scheme for multivariate analysis
SNPs associations with schizophrenia?
SNP associations with exposure to HSV-1, CMV or Tox
Interactions: SNP x HSV-1 exposure

8. Results
Associations with schizophrenia:
Five SNPs: p < 0.05, uncorrected; OR 0.41-0.79
SNP associations with infectious exposure:
rs3130297 associated with HSV-1 exposure (OR 4.76)
Interactions: SNP x HSV-1 exposure:
rs3130297 A allele: SZ; G allele: HSV-1

9. GWAS SNPs analyzed

10. A model for schizophrenia genesis
based on HLA associations
p < 0.05, uncorrected

11. Conclusions / Future Directions
 Validation of HLA associations with
schizophrenia risk among African-Americans
 Suggestive association with HSV-1 exposure
 Novel pleiotropic effect?
Ongoing studies:
 Independent replications
 Correlations with cognitive functions
 Brain imaging studies