{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T03:10:21Z","timestamp":1778296221464,"version":"3.51.4"},"posted":{"date-parts":[[2025,3,20]]},"group-title":"Genetic and Genomic Medicine","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Major Depressive Disorder is complex and moderately heritable, with heritability estimates ranging from 30% to 40%. Major depressive disorder (MDD) is a significant comorbidity in people living with HIV (PLWHIV), where it is associated with non-adherence to anti-retroviral treatment, increased risk of suicide-related behaviors among others. This study investigated the genetic risk loci associated with MDD among adult PLWHIV in Uganda.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The case-control study analyzed 282 samples (139 MDD cases and 143 controls), who were assessed for MDD using the Mini International Neuropsychiatric Interview. The DNA of study participants was genotyped at the Center for Proteomic and Genomic Research in South Africa using the H3Africa array (version2). Data were analyzed using PLINK2 and GEMMA softwares for quality control and genome-wide association analysis respectively, followed by functional mapping with FUMA software.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    While no significant single nucleotide polymorphisms (SNPs) were identified at the genome-wide threshold, three independent SNPs were found to be suggestively associated with MDD with the most significant being rs4375916 on chromosome 2 (p=1.086\u00d710\n                    <jats:sup>\u22127<\/jats:sup>\n                    ), followed by rs1075618 on chromosome 3 (p=3.093\u00d710\n                    <jats:sup>\u22127<\/jats:sup>\n                    ) and rs953855 on chromosome 13 (p=4.906\u00d710\n                    <jats:sup>\u22127<\/jats:sup>\n                    ). These SNPs have been found to be linkage disequilibrium (LD) with SNPs previously associated with other psychiatric conditions like Alzheimer\u2019s, alcohol use disorder, and bipolar disorder, although they have not previously been linked to MDD. Gene-set enrichment analysis revealed associations with key biological processes including synaptic organization suggesting potential involvement in the pathophysiology of MDD.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study provides preliminary evidence for genetic contributors to MDD in PLWHIV of African ancestry. While larger, adequately powered studies are needed, our findings emphasize the importance of investigating psychiatric genetics in HIV populations, where depression represents a critical comorbidity influencing treatment outcomes.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.19.25324246","type":"posted-content","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T16:12:13Z","timestamp":1742487133000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic Determinants of Major Depressive Disorder among Adult Persons Living With HIV in Uganda"],"prefix":"10.64898","author":[{"given":"Olga Nsangi","family":"Tendo","sequence":"first","affiliation":[{"name":"Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda"},{"name":"African Centers of Excellence in Bioinformatics and Data Intensive Sciences, Makerere University, Kampala, Uganda"},{"name":"Medical Research Council\/Uganda Virus Research Institute (MRC\/UVRI) and London School of Hygiene & Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Galiwango","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda"},{"name":"African Centers of Excellence in Bioinformatics and Data Intensive Sciences, Makerere University, Kampala, Uganda"},{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University, P.O Box 22418, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Kinyanda","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute (MRC\/UVRI) and London School of Hygiene & Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Sajatovic","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University School, Cleveland, Ohio, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Kaddumukasa","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kaddumukasa","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elly","family":"Katabira","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Nabbumba","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soraya","family":"Seedat","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"},{"name":"South African Medical Research Council\/Stellenbosch University Genomics of Brain Disorders Unit, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sian M.J.","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"},{"name":"South African Medical Research Council\/Stellenbosch University Genomics of Brain Disorders Unit, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Segun","family":"Fatumo","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute (MRC\/UVRI) and London School of Hygiene & Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda"},{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom"},{"name":"Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Kalungi","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute (MRC\/UVRI) and London School of Hygiene & Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe, Uganda"},{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom"},{"name":"Department of Medical Biochemistry, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050819351681000_2025.03.19.25324246v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.12"},{"key":"2026050819351681000_2025.03.19.25324246v2.2","unstructured":"World Health Organization, Depression and Other Common Mental Disorders: Global Health Estimates. 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