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Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study

Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample...

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Autores principales: Wu, Bang-Sheng, Zhang, Ya-Ru, Li, Hong-Qi, Kuo, Kevin, Chen, Shi-Dong, Dong, Qiang, Liu, Yong, Yu, Jin-Tai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443658/
https://www.ncbi.nlm.nih.gov/pubmed/34526483
http://dx.doi.org/10.1038/s41398-021-01599-x
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author Wu, Bang-Sheng
Zhang, Ya-Ru
Li, Hong-Qi
Kuo, Kevin
Chen, Shi-Dong
Dong, Qiang
Liu, Yong
Yu, Jin-Tai
author_facet Wu, Bang-Sheng
Zhang, Ya-Ru
Li, Hong-Qi
Kuo, Kevin
Chen, Shi-Dong
Dong, Qiang
Liu, Yong
Yu, Jin-Tai
author_sort Wu, Bang-Sheng
collection PubMed
description Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.
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spelling pubmed-84436582021-10-04 Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study Wu, Bang-Sheng Zhang, Ya-Ru Li, Hong-Qi Kuo, Kevin Chen, Shi-Dong Dong, Qiang Liu, Yong Yu, Jin-Tai Transl Psychiatry Article Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD. Nature Publishing Group UK 2021-09-15 /pmc/articles/PMC8443658/ /pubmed/34526483 http://dx.doi.org/10.1038/s41398-021-01599-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Bang-Sheng
Zhang, Ya-Ru
Li, Hong-Qi
Kuo, Kevin
Chen, Shi-Dong
Dong, Qiang
Liu, Yong
Yu, Jin-Tai
Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title_full Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title_fullStr Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title_full_unstemmed Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title_short Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
title_sort cortical structure and the risk for alzheimer’s disease: a bidirectional mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443658/
https://www.ncbi.nlm.nih.gov/pubmed/34526483
http://dx.doi.org/10.1038/s41398-021-01599-x
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