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Polygenic score analysis identifies distinct genetic risk profiles in Alzheimer’s disease comorbidities
Indexado
WoS WOS:001459315100032
Scopus SCOPUS_ID:105002818793
DOI 10.1038/S41598-025-95755-8
Año 2025
Tipo artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


Abstract



Alzheimer's disease (AD) is usually accompanied by comorbidities such as type 2 diabetes (T2D), epilepsy, major depressive disorder (MDD), and migraine headaches (MH) that can significantly affect patient management and progression. As AD, these comorbidities have their own cumulative common genetic risk component that can be explored in a single individual through polygenic scores. Utilizing data from the UK Biobank, we investigated the correlation between polygenic scores (PGS) for these comorbidities and their actual presentation in AD patients. We show that individuals with higher PGS values showed an elevated risk of developing T2D (OR 2.1, p = 1.07 x 10(-11)) and epilepsy (OR 1.5, p = 0.0176). High T2D-PGS is also associated with an earlier AD onset in individuals at high genetic risk for AD (AD-PGS). In contrast, no significant genetic associations were found for MDD and MH. Our findings show distinct common genetic risk factors for T2D and epilepsy carried by AD patients that are associated with increased prevalence and earlier disease onset. These results highlight the contribution of common genetic variation to the broader clinical landscape of AD and will contribute to future tailored patient management strategies for individuals at high genetic risk.

Revista



Revista ISSN
Scientific Reports 2045-2322

Métricas Externas



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Disciplinas de Investigación



WOS
Multidisciplinary Sciences
Scopus
Multidisciplinary
SciELO
Sin Disciplinas

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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional



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Autores - Afiliación



Ord. Autor Género Institución - País
1 Hernandez, Carlos F. - Universidad del Desarrollo - Chile
2 Villaman, Camilo - Universidad del Desarrollo - Chile
3 Leu, Costin - Univ Texas Hlth Sci Ctr Houston - Estados Unidos
UCL - Reino Unido
University of Texas Health Science Center at Houston - Estados Unidos
UCL Queen Square Institute of Neurology - Reino Unido
4 Lal, Dennis - Univ Texas Hlth Sci Ctr Houston - Estados Unidos
Broad Inst MIT & Harvard - Estados Unidos
Univ Cologne - Alemania
University of Texas Health Science Center at Houston - Estados Unidos
McGovern Medical School - Estados Unidos
Broad Institute - Estados Unidos
Medizinische Fakultät - Alemania
5 Mata, Ignacio - CLEVELAND CLIN - Estados Unidos
Cleveland Clinic Foundation - Estados Unidos
6 Klein, Andres D. Hombre Universidad del Desarrollo - Chile
7 Perez-Palma, Eduardo - Universidad del Desarrollo - Chile

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Financiamiento



Fuente
Fondo Nacional de Desarrollo Científico y Tecnológico
National Institutes of Health
Michael J. Fox Foundation for Parkinson's Research
Agencia Nacional de Investigación y Desarrollo
ANID FONDEQUIP
Chilean National Agency for Investigation and Development
Agencia Nacional de Investigacin y Desarrollo
ASAP-GP2

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos



Agradecimiento
This research has been conducted using the UK Biobank Resource under Application Number 81646. We thank UKB participants who consented to participate in this research and the researchers/employees who collected and contributed the data. We would like to thank the research participants and employees of 23andMe, Inc. for also helping to make this work possible.
Eduardo P\u00E9rez-Palma is supported by the Chilean National Agency for Investigation and Development (ANID), FONDECYT grant 1221464. Carlos Hern\u00E1ndez is supported by the Chilean National Agency for Investigation and Development, ANID (Beca Doctorado Nacional 2020 Folio 21201541). Computation provided by ANID FONDEQUIP EQM150093. Ignacio Mata is currently funded by the National Institutes of Health (1R01NS112499), Michael J. Fox Foundation and the Aligning Science Across Parkinson\u2019s Global Parkinson Genetic Program (ASAP-GP2).

Muestra la fuente de financiamiento declarada en la publicación.