Unravelling the genetic risk associated with major depressive disorder among an ethnically diverse African ancestry population

Abstract

Major depressive disorder (MDD), which is a significant contributor to the global health burden is characterised by a pervasive low mood and an inability to feel pleasure in normally pleasurable activities. Most MDD genetic studies have been carried out mainly on European ancestry populations limiting the generalisability of findings to non-European populations like the highly diverse African population. This study aimed to investigate the common genetic variants and other risk factors (sociodemographic, psychosocial, biological) associated with MDD among general out-patient participants from an African ancestry population attending the NeuroGAP study. A case-control study was carried out on 13,616 control participant data from the parent NeuroGAP study for whom phenotypic data was currently available and 653 of these participants also had genome wide association study (GWAS) data available. These participants were recategorised as MDD cases and MDD free controls using a Kessler psychological distress scale (K10) cut-off score of 13. The participant sample data was analysed using a GWAS pipeline generated using R software, a functional mapping and annotation tool (FUMA) and binomial regression for the phenotype analyses. The main GWAS findings in this study were the 107 significant single nucleotide polymorphisms (SNPs) (P =< 5X10-8) in 34 risk loci identified to be associated with MDD. The main findings from the phenotype analysis were that among these outpatient participants increasing negative life events, the physical comorbidity of arthritis, and the psychosomatic problems of chronic neck or back pain and frequent or severe headaches were the strongest independent determinants of MDD. These results suggest that psychosocial factors, physical comorbidities and psychosomatic complaints are major risk factors for MDD among an African ancestry population. The GWAS results suggest a possibility for novel MDD genetic risk loci discovery in African ancestry populations.