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Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging
Cognition in adults shows variation due to developmental and degenerative components. A recent genome-wide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlyin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428100/ https://www.ncbi.nlm.nih.gov/pubmed/30830859 http://dx.doi.org/10.18632/aging.101844 |
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author | Knol, Maria J. Heshmatollah, Alis Cremers, Lotte G.M. Ikram, M. Kamran Uitterlinden, André G. van Duijn, Cornelia M. Niessen, Wiro J. Vernooij, Meike W. Ikram, M. Arfan Adams, Hieab H.H. |
author_facet | Knol, Maria J. Heshmatollah, Alis Cremers, Lotte G.M. Ikram, M. Kamran Uitterlinden, André G. van Duijn, Cornelia M. Niessen, Wiro J. Vernooij, Meike W. Ikram, M. Arfan Adams, Hieab H.H. |
author_sort | Knol, Maria J. |
collection | PubMed |
description | Cognition in adults shows variation due to developmental and degenerative components. A recent genome-wide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlying these genetic variants by relating them to functional, clinical and neuroimaging outcomes. This study was conducted within the population-based Rotterdam Study (N=11,496, mean age 65.3±9.9 years, 58.0% female). We used lead variants for general cognitive function to construct a polygenic score (PGS), and additionally excluded developmental variants at multiple significance thresholds. A higher PGS was related to more years of education (β=0.29, p=4.3x10(-7)) and a larger intracranial volume (β=0.05, p=7.5x10(-4)). To a smaller extent, the PGS was associated with less cognitive decline (β(ΔG-factor)=0.03, p=1.3x10(-3)), which became non-significant after adjusting for education (p=1.6x10(-2)). No associations were found with daily functioning, dementia, parkinsonism, stroke or microstructural white matter integrity. Excluding developmental variants attenuated nearly all associations. In conclusion, this study suggests that the genetic variants identified for general cognitive function are acting mainly through the developmental pathway of cognition. Therefore, cognition, assessed cross-sectionally, seems to have limited value as a biomarker for neurodegeneration. |
format | Online Article Text |
id | pubmed-6428100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-64281002019-03-26 Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging Knol, Maria J. Heshmatollah, Alis Cremers, Lotte G.M. Ikram, M. Kamran Uitterlinden, André G. van Duijn, Cornelia M. Niessen, Wiro J. Vernooij, Meike W. Ikram, M. Arfan Adams, Hieab H.H. Aging (Albany NY) Research Paper Cognition in adults shows variation due to developmental and degenerative components. A recent genome-wide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlying these genetic variants by relating them to functional, clinical and neuroimaging outcomes. This study was conducted within the population-based Rotterdam Study (N=11,496, mean age 65.3±9.9 years, 58.0% female). We used lead variants for general cognitive function to construct a polygenic score (PGS), and additionally excluded developmental variants at multiple significance thresholds. A higher PGS was related to more years of education (β=0.29, p=4.3x10(-7)) and a larger intracranial volume (β=0.05, p=7.5x10(-4)). To a smaller extent, the PGS was associated with less cognitive decline (β(ΔG-factor)=0.03, p=1.3x10(-3)), which became non-significant after adjusting for education (p=1.6x10(-2)). No associations were found with daily functioning, dementia, parkinsonism, stroke or microstructural white matter integrity. Excluding developmental variants attenuated nearly all associations. In conclusion, this study suggests that the genetic variants identified for general cognitive function are acting mainly through the developmental pathway of cognition. Therefore, cognition, assessed cross-sectionally, seems to have limited value as a biomarker for neurodegeneration. Impact Journals 2019-03-04 /pmc/articles/PMC6428100/ /pubmed/30830859 http://dx.doi.org/10.18632/aging.101844 Text en Copyright © 2019 Knol et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Knol, Maria J. Heshmatollah, Alis Cremers, Lotte G.M. Ikram, M. Kamran Uitterlinden, André G. van Duijn, Cornelia M. Niessen, Wiro J. Vernooij, Meike W. Ikram, M. Arfan Adams, Hieab H.H. Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title | Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title_full | Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title_fullStr | Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title_full_unstemmed | Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title_short | Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
title_sort | genetic variation underlying cognition and its relation with neurological outcomes and brain imaging |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428100/ https://www.ncbi.nlm.nih.gov/pubmed/30830859 http://dx.doi.org/10.18632/aging.101844 |
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