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A genome-wide association meta-analysis of all-cause and vascular dementia

Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium

. 2024 ; 20 (9) : 5973-5995. [pub] 20240724

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, metaanalýza

Perzistentní odkaz   https://www.medvik.cz/link/bmc25004128

Grantová podpora
RC2 HL102419 NHLBI NIH HHS - United States
R01 AG054076 NIA NIH HHS - United States
AG033090 UT Health San Antonio Center for Biomedical Neuroscience
AG066524 UT Health San Antonio Center for Biomedical Neuroscience
RF1 AG061729 NIA NIH HHS - United States
R01 HL105756 NHLBI NIH HHS - United States
AG059421 UT Health San Antonio Center for Biomedical Neuroscience
R01 AG033193 NIA NIH HHS - United States
P30 AG059305 NIA NIH HHS - United States
R01HL105756 NHLBI NIH HHS - United States
R01 NS017950 NINDS NIH HHS - United States
UF1 NS125513 NINDS NIH HHS - United States
P30 AG066518 NIA NIH HHS - United States
RF1 AG061729A1 UT Health San Antonio Center for Biomedical Neuroscience
RF1 AG059421 NIA NIH HHS - United States
K01NS126489 NINDS NIH HHS - United States
AG049607 UT Health San Antonio Center for Biomedical Neuroscience
UF1NS125513 NINDS NIH HHS - United States
NS017950 NINDS NIH HHS - United States
RC2HL102419 NHLBI NIH HHS - United States
R01 AG049607 NIA NIH HHS - United States
5P30AG059305-03 UT Health San Antonio Center for Biomedical Neuroscience
R01 AG066524 NIA NIH HHS - United States
AG054076 UT Health San Antonio Center for Biomedical Neuroscience
P30 AG066546 NIA NIH HHS - United States
U01 AG052409 NIA NIH HHS - United States
5U01AG052409-04 UT Health San Antonio Center for Biomedical Neuroscience
K01 NS126489 NINDS NIH HHS - United States
AG033193 NIA NIH HHS - United States

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause 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. RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. HIGHLIGHTS: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.

Citace poskytuje Crossref.org

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