Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer's Disease Aetiopathogenesis in Men.
Alzheimer’s disease
CSF biomarkers
EADB
GR@ACE/DEGESCO
GWAS
Mendelian randomization
disease progression
mild cognitive impairment
mosaic loss of chromosome Y
polygenic risk score
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
04 Jan 2023
04 Jan 2023
Historique:
received:
04
11
2022
revised:
21
12
2022
accepted:
31
12
2022
entrez:
21
1
2023
pubmed:
22
1
2023
medline:
25
1
2023
Statut:
epublish
Résumé
Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer's disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (
Identifiants
pubmed: 36674414
pii: ijms24020898
doi: 10.3390/ijms24020898
pmc: PMC9863537
pii:
doi:
Substances chimiques
tau Proteins
0
Biomarkers
0
Amyloid beta-Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Centro de Investigación Biomédica en Red
ID : CNV-304-PRF-866
Organisme : Instituto de Salud Carlos III
ID : FI20/00215
Organisme : Ministerio Español de Ciencia, Innovación y Universidades
ID : FJC2018-036012-I
Organisme : Instituto de Salud Carlos III
ID : PI13/02434
Organisme : Instituto de Salud Carlos III
ID : PI16/01861
Organisme : Instituto de Salud Carlos III
ID : PI17/01474
Organisme : Instituto de Salud Carlos III
ID : PI19/01240
Organisme : Instituto de Salud Carlos III
ID : PI19/01301
Organisme : JPco-fuND
ID : FP-829-029
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