Polygenic prediction of major depressive disorder and related traits in African ancestries UK Biobank participants

Introduction Genome-Wide Association Studies (GWAS) over-represent European ancestries compared to the global population, neglecting all other ancestry groups and low-income nations. Consequently, polygenic risk scores (PRS) more accurately predict complex traits in Europeans than African Ancestries groups. Very few studies have looked at the transferability of European-derived PRS for behavioural and mental health phenotypes to non-Europeans. We assessed the comparative accuracy of PRS for Major Depressive Disorder (MDD) trained on European and African Ancestries GWAS studies to predict MDD and related traits in African Ancestries participants from the UK Biobank. Methods UK Biobank participants were selected based on Principal component analysis (PCA) clustering with an African genetic similarity reference population and MDD was assessed with the Composite International Diagnostic Interview (CIDI). Polygenic Risk Scores (PRS) were computed using PRSice2 using either European or African Ancestries GWAS summary statistics. Results PRS trained on European ancestry samples (246,363 cases) predicted case control status in Africans of the UK Biobank with similar accuracies (190 cases, R 2 =2%) to PRS trained on far much smaller samples of African Ancestries participants from 23andMe, Inc. (5045 cases, R 2 =1.8%). This suggests that prediction of MDD status from Africans to Africans had greater efficiency per unit increase in the discovery sample size than prediction of MDD from Europeans to Africans. Prediction of MDD status in African UK Biobank participants using GWAS findings of causal risk factors from European ancestries was non-significant. Conclusion GWAS studies of MDD in European ancestries are an inefficient means of improving polygenic prediction accuracy in African samples.