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| 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
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.
| 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
|
| 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 |
| 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). |