Background
Genome-wide association studies (GWAS) have identified several loci associated with
schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad
syndrome rather than within specific diagnostic categories.
Methods
1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder;
857 of their unaffected relatives, and 2739 healthy controls were genotyped with the
Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs
were conducted using UNPHASED, which combines information across families and unrelated
individuals. We attempted to replicate signals found in 23 genomic regions using existing
data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus
cohorts (10,352 schizophrenia patients and 24,474 controls).
Results
No individual SNP showed compelling evidence for association with psychosis in our
data. However, we observed a trend for association with same risk alleles at loci
previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium’s
panel of SNPs associated with schizophrenia significantly predicted disease status
in our sample (p = 5 × 10–14) and explained approximately 2% of the phenotypic variance.
Conclusions
Although narrowly defined phenotypes have their advantages, we believe new loci may
also be discovered through meta-analysis across broad phenotypes. The novel statistical
methodology we introduced to model effect size heterogeneity between studies should
help future GWAS that combine association evidence from related phenotypes. Applying
these approaches, we highlight three loci that warrant further investigation. We found
that SNPs conveying risk for schizophrenia are also predictive of disease status in
our data.
Key Words
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Article info
Publication history
Published online: July 19, 2013
Accepted:
March 30,
2013
Received in revised form:
March 27,
2013
Received:
October 23,
2012
Identification
Copyright
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