Genetic risk for major depressive disorder among three ethnically diverse African cohorts

Whereas we are aware of the roles genetics play in the development of major depressive disorder (MDD) (mainly from research among Caucasian populations), there remains a dearth in literature about specific genes affecting susceptibility among continental Africans. Moreover, African ancestry individuals harbour marked genetic diversity compared to persons from the rest of the world. To address this gap, I propose to investigate the genetic risk factors for MDD among continental Africans by (i) performing a genome-wide association study of MDD among pooled data from three ethnically diverse African cohorts (GPC, NeuroGAP and DepGenAfrica cohorts, n~23,776), (ii) replicate findings in an African/African-admixed PGC Cohort (n=198,497), (iii) meta-analyse findings from these combined cohorts (n~23,776 + n=198,497) and (iv) combine these results with the rest of the MDD PGC dataset (n~23,776, n=198,497 and n=1,622,192) in a final meta-analysis. Transferability of variants and MDD polygenic risk scores between the continental African cohort and PGC cohorts will also be determined. In the continental Africans dataset, causal relations for MDD will be investigated and a machine learning model for prediction of MDD will be built. This study has potential to identify mechanistic pathways and ultimately lead to development of new molecules or drug targets for MDD.