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Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors

Late-onset Alzheimer’s disease (AD) has a significant genetic and immunological component, but the molecular mechanisms through which genetic and immunity-related risk factors and their interplay contribute to AD pathogenesis are unclear. Therefore, we screened for genetic sharing between AD and the...

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Detalles Bibliográficos
Autores principales: van der Linden, Robert J., De Witte, Ward, Poelmans, Geert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226721/
https://www.ncbi.nlm.nih.gov/pubmed/34198788
http://dx.doi.org/10.3390/genes12060865
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author van der Linden, Robert J.
De Witte, Ward
Poelmans, Geert
author_facet van der Linden, Robert J.
De Witte, Ward
Poelmans, Geert
author_sort van der Linden, Robert J.
collection PubMed
description Late-onset Alzheimer’s disease (AD) has a significant genetic and immunological component, but the molecular mechanisms through which genetic and immunity-related risk factors and their interplay contribute to AD pathogenesis are unclear. Therefore, we screened for genetic sharing between AD and the blood levels of a set of cytokines and growth factors to elucidate how the polygenic architecture of AD affects immune marker profiles. For this, we retrieved summary statistics from Finnish genome-wide association studies of AD and 41 immune marker blood levels and assessed for shared genetic etiology, using a polygenic risk score-based approach. For the blood levels of 15 cytokines and growth factors, we identified genetic sharing with AD. We also found positive and negative genetic concordances—implying that genetic risk factors for AD are associated with higher and lower blood levels—for several immune markers and were able to relate some of these results to the literature. Our results imply that genetic risk factors for AD also affect specific immune marker levels, which may be leveraged to develop novel treatment strategies for AD.
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spelling pubmed-82267212021-06-26 Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors van der Linden, Robert J. De Witte, Ward Poelmans, Geert Genes (Basel) Article Late-onset Alzheimer’s disease (AD) has a significant genetic and immunological component, but the molecular mechanisms through which genetic and immunity-related risk factors and their interplay contribute to AD pathogenesis are unclear. Therefore, we screened for genetic sharing between AD and the blood levels of a set of cytokines and growth factors to elucidate how the polygenic architecture of AD affects immune marker profiles. For this, we retrieved summary statistics from Finnish genome-wide association studies of AD and 41 immune marker blood levels and assessed for shared genetic etiology, using a polygenic risk score-based approach. For the blood levels of 15 cytokines and growth factors, we identified genetic sharing with AD. We also found positive and negative genetic concordances—implying that genetic risk factors for AD are associated with higher and lower blood levels—for several immune markers and were able to relate some of these results to the literature. Our results imply that genetic risk factors for AD also affect specific immune marker levels, which may be leveraged to develop novel treatment strategies for AD. MDPI 2021-06-05 /pmc/articles/PMC8226721/ /pubmed/34198788 http://dx.doi.org/10.3390/genes12060865 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van der Linden, Robert J.
De Witte, Ward
Poelmans, Geert
Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title_full Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title_fullStr Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title_full_unstemmed Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title_short Shared Genetic Etiology between Alzheimer’s Disease and Blood Levels of Specific Cytokines and Growth Factors
title_sort shared genetic etiology between alzheimer’s disease and blood levels of specific cytokines and growth factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226721/
https://www.ncbi.nlm.nih.gov/pubmed/34198788
http://dx.doi.org/10.3390/genes12060865
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