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Chunk #14 — Materials and methods — Statistical analyses — Polygenic risk score analysis

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Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.
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Additional analyses were conducted to test whether extraversion could be predicted in an independent target cohort based on the GWA meta-analysis results. The target cohort was the Netherlands Twin Register (NTR) cohort (8648 subjects). Polygenic risk scores for this cohort were estimated using LDpred (Vilhjalmsson et al. 2015) that takes into account linkage disequilibrium among the SNPs. The estimation was based on a GWA meta-analysis in which the NTR and NESDA cohorts were excluded (further referred to as the discovery set). With the LD-corrected polygenic risk scores, generalized estimating equation (GEE) modeling was applied to test whether the polygenic risk scores predicted extraversion in the target cohort. The covariates age, sex and ten PCs were included as fixed effects in the model. The model also included a random intercept with family number as the cluster variable, to account for dependency among family members. Outliers on the PCs, including ethnic outliers, were excluded from the analysis.