Tendo Olga Nsangi, Galiwango Ronald, Kinyanda Eugene, Sajatovic Martha, Kaddumukasa Mark, Kaddumukasa Martin, Katabira Elly, Nabbumba Catherine, Soraya Seedat, Hemmings Sian, Kalungi Allan
Department of Immunology and Molecular Biology, Makerere University, P.O.Box 7072, Kampala, Uganda.
African Centers of Excellence in Bioinformatics and Data Intensive Sciences, Kampala, Uganda.
medRxiv. 2025 Mar 20:2025.03.19.25324246. doi: 10.1101/2025.03.19.25324246.
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.
重度抑郁症（MDD）具有遗传成分，遗传度估计在30%至40%之间。抑郁症是人类免疫缺陷病毒感染者（PLWHIV）中的一种重要合并症，会增加自杀相关行为的风险。本研究调查了乌干达成年HIV感染者中与MDD相关的遗传风险位点，该国关于这种关系的数据有限。
这项病例对照研究分析了282个样本（139例MDD病例和143例对照），在基线、六个月和一年时使用迷你国际神经精神访谈评估MDD情况。在这些时间点采集血样，在南非使用H3Africa芯片进行DNA基因分型。分别使用PLINK2和GEMMA进行质量控制和全基因组关联分析，随后使用FUMA进行功能定位分析。
虽然在全基因组阈值下未发现显著的单核苷酸多态性（SNP），但发现有六个SNP与MDD存在提示性关联。这些SNP与阿尔茨海默病、酒精使用障碍和双相情感障碍等其他精神疾病有关，此前未与MDD相关联。
该研究表明在PLWHIV和非洲血统人群中发现新型MDD遗传风险位点具有潜力，尤其是样本量更大时。
