Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiere

Bibliographic Details
Authors: García-González, Pablo, Bullido Gómez-Heras, María Jesús
Format: article
Publication Date:2023
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/706833
Online Access:http://hdl.handle.net/10486/706833
https://dx.doi.org/10.3390/ijms24020898
Access Level:Open access
Keyword:CSF biomarkers
EADB
GR@ACE/DEGESCO
GWAS
Mendelian randomization
Alzheimer’s Disease
Disease Progression
Mild Cognitive Impairment
Mosaic Loss of Chromosome Y
Polygenic Risk Score
Biología y Biomedicina / Biología
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repository_id_str
spelling Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in menGarcía-González, PabloBullido Gómez-Heras, María JesúsCSF biomarkersEADBGR@ACE/DEGESCOGWASMendelian randomizationAlzheimer’s DiseaseDisease ProgressionMild Cognitive ImpairmentMosaic Loss of Chromosome YPolygenic Risk ScoreBiología y Biomedicina / BiologíaArtículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiereMosaic 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 (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesisMDPIDepartamento de Biología MolecularFacultad de Ciencias20232023-01-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/706833https://dx.doi.org/10.3390/ijms24020898reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7068332026-06-23T12:46:27Z
dc.title.none.fl_str_mv Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
title Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
spellingShingle Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
García-González, Pablo
CSF biomarkers
EADB
GR@ACE/DEGESCO
GWAS
Mendelian randomization
Alzheimer’s Disease
Disease Progression
Mild Cognitive Impairment
Mosaic Loss of Chromosome Y
Polygenic Risk Score
Biología y Biomedicina / Biología
title_short Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
title_full Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
title_fullStr Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
title_full_unstemmed Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
title_sort Mendelian randomisation confirms the role of Y-chromosome loss in Alzheimer’s disease aetiopathogenesis in men
dc.creator.none.fl_str_mv García-González, Pablo
Bullido Gómez-Heras, María Jesús
author García-González, Pablo
author_facet García-González, Pablo
Bullido Gómez-Heras, María Jesús
author_role author
author2 Bullido Gómez-Heras, María Jesús
author2_role author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv CSF biomarkers
EADB
GR@ACE/DEGESCO
GWAS
Mendelian randomization
Alzheimer’s Disease
Disease Progression
Mild Cognitive Impairment
Mosaic Loss of Chromosome Y
Polygenic Risk Score
Biología y Biomedicina / Biología
topic CSF biomarkers
EADB
GR@ACE/DEGESCO
GWAS
Mendelian randomization
Alzheimer’s Disease
Disease Progression
Mild Cognitive Impairment
Mosaic Loss of Chromosome Y
Polygenic Risk Score
Biología y Biomedicina / Biología
description Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiere
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-04
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/706833
https://dx.doi.org/10.3390/ijms24020898
url http://hdl.handle.net/10486/706833
https://dx.doi.org/10.3390/ijms24020898
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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