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Pairwise common variant meta-analyses of schizophrenia with other psychiatric disorders reveals shared and distinct gene and gene-set associations.

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 (P_Meta < 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.

SUBMITTER: Reay WR

PROVIDER: S-EPMC7217970 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pairwise common variant meta-analyses of schizophrenia with other psychiatric disorders reveals shared and distinct gene and gene-set associations.

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