A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation

Psychosis Endophenotypes International Consortium, Wellcome Trust Case-Control Consortium and Brown, Matthew A. (2014) A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation. Biological Psychiatry, 75 5: 386-397. doi:10.1016/j.biopsych.2013.03.033

Author Psychosis Endophenotypes International Consortium
Wellcome Trust Case-Control Consortium
Brown, Matthew A.
Title A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2014-03-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2013.03.033
Open Access Status Not Open Access
Volume 75
Issue 5
Start page 386
End page 397
Total pages 12
Place of publication Philadelphia, United States
Publisher Elsevier
Language eng
Subject 2803 Biological Psychiatry
Formatted abstract
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.
Keyword Bipolar disorder
Genome-wide association
Polygenic score analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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