دورية أكاديمية
Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men
| العنوان: | Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men |
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| المؤلفون: | García-González, Pablo, Rojas, Itziar de, Moreno-Grau, Sonia, Montrreal, Laura, Puerta, Raquel, Alarcón-Martín, Emilio, Quintela, Inés, Orellana, Adela, Andrade, Victor, Martino Adami, Pamela V., Heilmann-Heimbach, Stefanie, Gómez-Garre, Pilar, Periñán, María Teresa, Alvarez, Ignacio, Díez-Fairen, Mónica, Nuñez Llaves, Raul, Olivé Roig, Claudia, García-Ribas, Guillermo, Menéndez-González, Manuel, Martínez, Carmen, Aguilar, Miquel, Buongiorno, Mariateresa, Franco-Macías, Emilio, Saez, Maria Eugenia, Cano, Amanda, Bullido Gómez-Heras, Maria Jesús, Real-Navarrete, Luis Miguel, Rodríguez-Rodríguez, Eloy, Royo-Sánchez-Palencia, José Luis, Álvarez, Victoria, Pastor, Pau, Piñol-Ripoll, Gerard, Mir, Pablo, Calero Lara, Miguel, Medina Padilla, Miguel, Sánchez-Juan, Pascual, Carracedo Álvarez, Ángel María, Valero, Sergi, Hernández, Isabel, Tàrraga, Lluis, Ramirez, Alfredo, Boada, Mercé, Ruiz Laza, Agustín |
| بيانات النشر: | IOAP-MDPI |
| سنة النشر: | 2023 |
| المجموعة: | RIUMA - Repositorio Institucional de la Universidad de Málaga |
| مصطلحات موضوعية: | Alzheimer, Enfermedad de, Alzheimer’s disease, Mosaic loss of chromosome Y, Disease progression, GWAS, Mendelian randomization, GR@ACE/DEGESCO, EADB, Mild cognitive impairment, Polygenic risk score, CSF biomarkers |
| الوصف: | 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 (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 pathogenesis. ; P.G.-G. (Pablo García-González) is supported by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). I.d.R is supported by a national grant from the Instituto de Salud Carlos III FI20/00215. A.C. (Amanda Cano) acknowledges the support of the Spanish Ministry of Science, Innovation, and Universities under the grant Juan de la Cierva (FJC2018-036012-I). M.B. (Mercé Boada) and A.R. (Agustín Ruiz) are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. Acción Estratégica en Salud is integrated into the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | García-González P, de Rojas I, Moreno-Grau S, Montrreal L, Puerta R, Alarcón-Martín E, Quintela I, Orellana A, Andrade V, Adami PVM, Heilmann-Heimbach S, Gomez-Garre P, Periñán MT, Alvarez I, Diez-Fairen M, Nuñez Llaves R, Olivé Roig C, Garcia-Ribas G, Menéndez-González M, Martínez C, Aguilar M, Buongiorno M, Franco-Macías E, Saez ME, Cano A, Bullido MJ, Real LM, Rodríguez-Rodríguez E, Royo JL, Álvarez V, Pastor P, Piñol-Ripoll G, Mir P, Lara MC, Padilla MM, Sánchez-Juan P, Carracedo A, Valero S, Hernandez I, Tàrraga L, Ramirez A, Boada M, Ruiz A. Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men. International Journal of Molecular Sciences. 2023; 24(2):898. https://doi.org/10.3390/ijms24020898Test; https://hdl.handle.net/10630/25996Test; https://doi.org/10.3390/ijms24020898Test |
| DOI: | 10.3390/ijms24020898 |
| الإتاحة: | https://doi.org/10.3390/ijms24020898Test https://hdl.handle.net/10630/25996Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Atribución 4.0 Internacional |
| رقم الانضمام: | edsbas.72F7C946 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms24020898 |
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