Pathomechanisms and Signatures in the Longitudinal Course of Psychosis



013_ Novel tissue-specific functional risk score model using eQTL prior in cross-disorders

Research Question and Aims

We are establishing a novel method to derive tissue-specific functional risk scores in psychiatric disorders using an eQTL prior. We establish the new scoring in a small cohort for which postmortem brain gene and exon expression is available. We seek to validate our results on a larger cross-disorder cohort of Psycourse and assess association of the novel score with phenotype information obtained from questionnaire data (visit 1).

Analytic Plan

Polygenic risk scores (PRS) will be constructed from the qced and imputed PsyCourse genotypes and summary statistics of the recent GWAS for psychiatric disorders. Polygenic risk scores will be created by using LDpred and tissue-specific functional risk scores will be created with our new method by integrating an eQTL prior.
Regression models will be used to test for main effects of these risk scores (functional genetic risk score and the PRS) on psychiatric outcomes (e.g., presence of psychiatric symptoms as measured by the DSM-IV Diagnosis and Symptom rating scales (PANSS, GAF or YMRS) and questionnaires (BDI-II, LEQ, WHOQOL-BREF). All models will be adjusted for relevant covariates including age, sex and the first principal components of the SNP-array based population stratification analysis.

Resources needed

We will require imputed and quality controlled SNP data and their relevant phenotype data, including, chip and imputation batches as well as factors to correct for population stratification.