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A genome-wide association meta-analysis of all-cause and vascular dementia
Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, metaanalýza
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
NLK
PubMed Central
od 2024
ProQuest Central
od 2024-01-01
Nursing & Allied Health Database (ProQuest)
od 2024-01-01
Health & Medicine (ProQuest)
od 2024-01-01
Family Health Database (ProQuest)
od 2024-01-01
Wiley-Blackwell Open Access Titles
od 2024
ROAD: Directory of Open Access Scholarly Resources
od 2005
PubMed
39046104
DOI
10.1002/alz.14115
Knihovny.cz E-zdroje
- MeSH
- Alzheimerova nemoc genetika MeSH
- celogenomová asociační studie * MeSH
- demence genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- lidé MeSH
- rizikové faktory MeSH
- vaskulární demence * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
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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