{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Cook N"],"funding":["BLRD VA","NIA NIH HHS"],"pubmed_abstract":["Sex differences are pervasive in Alzheimer's disease, but the underlying drivers remain poorly understood. To address this, we performed sex-stratified genome-wide association studies of Alzheimer's disease in ~1,000,000 individuals, which we subsequently integrated with proteogenomics datasets from neurological tissues to identify candidate causal genes. We further prioritized genes through additional multi-omics approaches, including quantitative trait locus summary-based mendelian randomization and colocalization. Altogether, we prioritized 125 female-biased and 21 male-biased risk genes. Female-biased pathways included amyloid, neurite, stress, clearance, and immune processes, with genes enriched for microglia and astrocyte expression. Through computational drug repurposing analyses, a set of sex hormone related drugs, converging on <i>Epidermal Growth Factor Receptor</i> (<i>EGFR</i>), were uniquely prioritized in women. Finally, we identified <i>Haptoglobin</i> (<i>HP</i>) as a female-specific gene, leveraging long-read sequencing approaches to implicate a link to oxidative stress, APOE, and hemoglobin biology. Altogether, our findings provide a portal into sex-specific precision medicine for Alzheimer's disease."],"journal":["medRxiv : the preprint server for health sciences"],"pagination":["2025.10.31.25339089"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636628"],"repository":["biostudies-literature"],"pubmed_title":["Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease."],"pmcid":["PMC12636628"],"funding_grant_id":["IK4 BX005219","R01 AG089509","R01 AG071706","I01 BX005686","R01 AG072120","R01 AG075827","R00 AG075238","R01 AG064614","R01 AG078964","R01 AG074007","R00 AG071837","R01 AG058501"],"pubmed_authors":["Le Guen Y","Altmann A","Young C","Napolioni V","Wingo AP","Talozzi L","Zeng Y","Yang C","Western D","FinnGen","Mormino EC","Cruchaga C","Belloy ME","Liu Y","Cook N","Stewart I","Wingo TS","He Z","Song S","Greicius MD","Sivasankaran SK","Sung YJ"],"additional_accession":[]},"is_claimable":false,"name":"Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease.","description":"Sex differences are pervasive in Alzheimer's disease, but the underlying drivers remain poorly understood. To address this, we performed sex-stratified genome-wide association studies of Alzheimer's disease in ~1,000,000 individuals, which we subsequently integrated with proteogenomics datasets from neurological tissues to identify candidate causal genes. We further prioritized genes through additional multi-omics approaches, including quantitative trait locus summary-based mendelian randomization and colocalization. Altogether, we prioritized 125 female-biased and 21 male-biased risk genes. Female-biased pathways included amyloid, neurite, stress, clearance, and immune processes, with genes enriched for microglia and astrocyte expression. Through computational drug repurposing analyses, a set of sex hormone related drugs, converging on <i>Epidermal Growth Factor Receptor</i> (<i>EGFR</i>), were uniquely prioritized in women. Finally, we identified <i>Haptoglobin</i> (<i>HP</i>) as a female-specific gene, leveraging long-read sequencing approaches to implicate a link to oxidative stress, APOE, and hemoglobin biology. Altogether, our findings provide a portal into sex-specific precision medicine for Alzheimer's disease.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-10T03:14:06.965Z","creation":"2026-06-10T03:07:55.254Z"},"accession":"S-EPMC12636628","cross_references":{"pubmed":["41282793"],"doi":["10.1101/2025.10.31.25339089"]}}