Genetic Determinants Of Major Depressive Disorder (MDD) Among Adult Persons Living With HIV In Uganda

Major Depressive Disorder (MDD) has a heritable component, with estimates of heritability ranging from 30% to 40%. Depression is a significant comorbidity in people living with HIV (PLWHIV), increasing the risk of suicide-related behaviors. This study investigated the genetic risk loci associated with MDD among adults living with HIV in Uganda, where limited data exist on this relationship.

The case-control study analyzed 282 samples (139 MDD cases and 143 controls), assessed for MDD at baseline, six months, and one year using the Mini International Neuropsychiatric Interview. Blood samples were collected at these intervals, with DNA genotyping conducted in South Africa using the H3Africa array. Data were analyzed using PLINK2 and GEMMA for quality control and genome-wide association analysis respectively, followed by functional mapping with FUMA.

While no significant single nucleotide polymorphisms (SNPs) were identified at the genome-wide threshold, six SNPs were found to be suggestively associated with MDD. These SNPs, which have been associated with other psychiatric conditions like Alzheimer's, alcohol use disorder, and bipolar disorder and have not previously been linked to MDD.

The study suggests the potential for novel MDD genetic risk loci discovery in PLWHIV and people of African ancestry, especially with larger sample sizes.