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Polygenic predictors of age-related decline in cognitive ability

Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and psychological factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age...

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Autores principales: Ritchie, Stuart J., Hill, W. David, Marioni, Riccardo E., Davies, Gail, Hagenaars, Saskia P., Harris, Sarah E., Cox, Simon R., Taylor, Adele M., Corley, Janie, Pattie, Alison, Redmond, Paul, Starr, John M., Deary, Ian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515838/
https://www.ncbi.nlm.nih.gov/pubmed/30760887
http://dx.doi.org/10.1038/s41380-019-0372-x
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author Ritchie, Stuart J.
Hill, W. David
Marioni, Riccardo E.
Davies, Gail
Hagenaars, Saskia P.
Harris, Sarah E.
Cox, Simon R.
Taylor, Adele M.
Corley, Janie
Pattie, Alison
Redmond, Paul
Starr, John M.
Deary, Ian J.
author_facet Ritchie, Stuart J.
Hill, W. David
Marioni, Riccardo E.
Davies, Gail
Hagenaars, Saskia P.
Harris, Sarah E.
Cox, Simon R.
Taylor, Adele M.
Corley, Janie
Pattie, Alison
Redmond, Paul
Starr, John M.
Deary, Ian J.
author_sort Ritchie, Stuart J.
collection PubMed
description Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and psychological factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70, and cognitive change from age 70 to age 79, in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within older age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initial n = 1091 age 70; final n = 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We ran additional analyses using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardized β-values = –0.178 to 0.302), and the polygenic score for education was associated with cognitive change from childhood to age 70 (standardized β = 0.100). No polygenic scores were statistically significantly associated with variation in cognitive change between ages 70 and 79, and effect sizes were small. However, APOE e4 status made a significant prediction of the rate of cognitive decline from age 70 to 79 (standardized β = –0.319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par with APOE e4, a better-established predictor.
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spelling pubmed-75158382020-09-29 Polygenic predictors of age-related decline in cognitive ability Ritchie, Stuart J. Hill, W. David Marioni, Riccardo E. Davies, Gail Hagenaars, Saskia P. Harris, Sarah E. Cox, Simon R. Taylor, Adele M. Corley, Janie Pattie, Alison Redmond, Paul Starr, John M. Deary, Ian J. Mol Psychiatry Article Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and psychological factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70, and cognitive change from age 70 to age 79, in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within older age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initial n = 1091 age 70; final n = 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We ran additional analyses using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardized β-values = –0.178 to 0.302), and the polygenic score for education was associated with cognitive change from childhood to age 70 (standardized β = 0.100). No polygenic scores were statistically significantly associated with variation in cognitive change between ages 70 and 79, and effect sizes were small. However, APOE e4 status made a significant prediction of the rate of cognitive decline from age 70 to 79 (standardized β = –0.319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par with APOE e4, a better-established predictor. Nature Publishing Group UK 2019-02-13 2020 /pmc/articles/PMC7515838/ /pubmed/30760887 http://dx.doi.org/10.1038/s41380-019-0372-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ritchie, Stuart J.
Hill, W. David
Marioni, Riccardo E.
Davies, Gail
Hagenaars, Saskia P.
Harris, Sarah E.
Cox, Simon R.
Taylor, Adele M.
Corley, Janie
Pattie, Alison
Redmond, Paul
Starr, John M.
Deary, Ian J.
Polygenic predictors of age-related decline in cognitive ability
title Polygenic predictors of age-related decline in cognitive ability
title_full Polygenic predictors of age-related decline in cognitive ability
title_fullStr Polygenic predictors of age-related decline in cognitive ability
title_full_unstemmed Polygenic predictors of age-related decline in cognitive ability
title_short Polygenic predictors of age-related decline in cognitive ability
title_sort polygenic predictors of age-related decline in cognitive ability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515838/
https://www.ncbi.nlm.nih.gov/pubmed/30760887
http://dx.doi.org/10.1038/s41380-019-0372-x
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