2025-02-17

097_ Psychiatric Genomics Consortium Schizophrenia GWAS

Research Question and Aims

The PsyCourse data requested in this proposal will be part of the next genome-wide association studies (GWAS) of schizophrenia conducted by the Psychiatric Genomics Consortium (PGC) as well as downstream analyses.
The key aims of this project are to advance discovery for schizophrenia by employing several analytical approaches. First, it seeks to enhance genetic discovery through a GWAS meta-analysis that includes large cohorts and biobanks representing diverse ancestral populations. Second, it aims to improve understanding of genetic architecture by integrating both common and rare genetic variations. Third, it plans to advance discovery beyond standard diagnostic definitions by developing phenotypic instruments that enable wellpowered, global trans-diagnostic studies. These studies aim to address critical questions about psychiatric disorders, such as: Do few vs many genetic factors underly clinical presentations? How do genetic effects impact common clinical outcomes? How do genetic effects vary through life? Finally, this project aims to increase the impact of genomic findings on novel therapeutic and preventative opportunities by fine-mapping and integrating functional genomic data with PGC-SCZ results. This includes identifying modifiable causal risk factors through Mendelian Randomization and using polygenic modeling in combination with epidemiological data to improve patient stratification and outcome prediction.

Analytic Plan

The PsyCourse data will be analyzed alongside other cohorts in the PGC Schizophrenia Working Group, following the analytic approach from our previous GWAS meta-analysis (PMID: 35396580). This includes standard quality control (using the RICOPILI pipeline or equivalent), genotype imputation, and case-control GWAS, followed by meta-analysis. Population stratification and other covariates will be considered in the analysis.
Sharing individual genotype data with the PGC-SCZ working group would allow inclusion of PsyCourse data in downstream post-GWAS analyses. If individual genotype data cannot be shared, we will provide standard GWAS protocols for QC and analysis and request that summary-level data to be shared with the group.

Resources needed

Genome-wide genotypes in PLINK format (pre-QC).