Abstract
The complex aetiology of schizophrenia is postulated to share components with other psychiatric disorders. We investigated pleiotropy amongst the common variant genomics of schizophrenia and seven other psychiatric disorders using a multimarker association test. Transcriptomic imputation was then leveraged to investigate the functional significance of variation mapped to these genes, prioritising several interesting functional candidates. Gene-based analysis of common variation revealed 67 schizophrenia-associated genes shared with other psychiatric phenotypes, including bipolar disorder, major depressive disorder, ADHD and autism-spectrum disorder. In addition, we uncovered 78 genes significantly enriched with common variant associations for schizophrenia that were not linked to any of these seven disorders (P > 0.05). Multivariable gene-set association suggested that common variation enrichment within biologically constrained genes observed for schizophrenia also occurs across several psychiatric phenotypes. Pairwise meta-analysis of schizophrenia and each psychiatric phenotype was implemented and identified 330 significantly associated genes (PMeta < 2.7 × 10−6) that were only nominally associated with each disorder individually (P < 0.05). These analyses consolidate the overlap between the genomic architecture of schizophrenia and other psychiatric disorders, uncovering several candidate pleiotropic genes which warrant further investigation.
Highlights
Schizophrenia is a psychiatric disorder which is proposed to arise from a complex interplay between heritable and environmental factors
Considering genes outside the extended major histocompatibility complex (MHC) region, 456 genes were associated with schizophrenia below the Bonferroni threshold (P < 2.7 × 10−6, Supplementary Table 1)
We investigated the association of the 456 genes which survived Bonferroni correction in the schizophrenia
Summary
Schizophrenia is a psychiatric disorder which is proposed to arise from a complex interplay between heritable and environmental factors. The genomic architecture of schizophrenia encompasses variation throughout the genome which have population frequencies ranging from common to ultra-rare[1,2,3,4]. The diagnostic boundaries between schizophrenia and other psychiatric disorders remain difficult to define. Psychiatric comorbidities are common in patients with schizophrenia[5], while the defined clinical presentation of the disorder itself resembles that of other diagnoses. Major depressive disorder (MDD) diagnosis is prevalent amongst individuals with schizophrenia[6,7]. Negative symptoms inherent to schizophrenia, which include avolition and asociality, are closely
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