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Yet, most genome\u2010wide association studies (GWAS) focus on AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We conducted a GWAS of all\u2010cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>For ACD, novel loci identified were associated with energy transport (<jats:italic>SEMA4D<\/jats:italic>), neuronal excitability (<jats:italic>ANO3<\/jats:italic>), amyloid deposition in the brain (<jats:italic>RBFOX1<\/jats:italic>), and magnetic resonance imaging markers of small vessel disease (SVD; <jats:italic>HBEGF<\/jats:italic>). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (<jats:italic>SPRY2<\/jats:italic>, <jats:italic>FOXA2<\/jats:italic>, <jats:italic>AJAP1<\/jats:italic>, and <jats:italic>PSMA3<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We conducted the largest genome\u2010wide association study of all\u2010cause dementia (ACD) and vascular dementia (VaD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Known genetic variants associated with AD were replicated for ACD and VaD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Functional analyses identified novel loci for ACD and VaD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14115","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T07:32:45Z","timestamp":1721806365000},"page":"5973-5995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["A genome\u2010wide association meta\u2010analysis of all\u2010cause and vascular dementia"],"prefix":"10.1002","volume":"20","author":[{"name":"The Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) 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