Pathomechanisms and Signatures in the Longitudinal Course of Psychosis



002_ Investigating the association of educational attainment polygenic risk scores with cognitive performance in the PsyCourse cohort

Research Question and Aims

The aim of this study is to investigate the association of educational attainment polygenic risk scores with various measures of cognitive performance in the PsyCourse cohort. It would also be of interest to compare how the educational attainment risk scores compare to bipolar or schizophrenia polygenic risk scores in explaining variance in cognitive performance.

Analytic Plan

We hypothesize that PRSEDU will have a significant effect on cognitive performance.
Data from all patients in PsyCourse who have genotype data available will be included in this study.

Polygenic risk scores:
GWAS summary statistics for educational attainment will be obtained from the Social Science Genetic Association Consortium (
1 The PRSEDU will be calculated based on summary statistics from the discovery dataset excluding rare SNPs (MAF < 5%), low quality imputed variants (info score <90%), indels, ambiguous markers (A/T and C/G), and SNPs in the extended major histocompatibility complex region (chromosome 6: 25-34 Mbp). Data will be clumped in windows of 500 kbp, discarding variants in LD (R2>.1) with another more significant marker. Polygenic risk scores will be standardized. Scores will be calculated based on p value thresholds ranging from p < 5 x 10-8 to p < 1. 2

Statistical analysis:
At each time point models will be built adjusting for age, sex, socioeconomic status, and psychopathology to determine the association of PRSEDU on cognitive performance as an outcome. To control for population stratification, we will adjust for the significantly associated principle components.

Resources needed

Sociodemographic, cognitive performance variables and measures of psychopathology will be used along with genotyping data. Readily available PRSBP and PRSSZ may also be used.