The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses
dc.contributor.author | Walker, RM | |
dc.contributor.author | Chong, M | |
dc.contributor.author | Perrot, N | |
dc.contributor.author | Pigeyre, M | |
dc.contributor.author | Gadd, DA | |
dc.contributor.author | Stolicyn, A | |
dc.contributor.author | Shi, L | |
dc.contributor.author | Campbell, A | |
dc.contributor.author | Shen, X | |
dc.contributor.author | Whalley, HC | |
dc.contributor.author | Nevado-Holgado, A | |
dc.contributor.author | McIntosh, AM | |
dc.contributor.author | Heitmeier, S | |
dc.contributor.author | Rangarajan, S | |
dc.contributor.author | O'Donnell, M | |
dc.contributor.author | Smith, EE | |
dc.contributor.author | Yusuf, S | |
dc.contributor.author | Whiteley, WN | |
dc.contributor.author | Paré, G | |
dc.date.accessioned | 2024-06-03T14:56:10Z | |
dc.date.issued | 2024-05-18 | |
dc.date.updated | 2024-04-23T14:02:57Z | |
dc.description.abstract | Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins’ plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8–19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline. | en_GB |
dc.identifier.citation | Vol. 14, article 204 | en_GB |
dc.identifier.doi | 10.1038/s41398-024-02915-x | |
dc.identifier.uri | http://hdl.handle.net/10871/136110 | |
dc.identifier | ORCID: 0000-0002-1060-4479 (Walker, Rosie May) | |
dc.identifier | ScopusID: 23029293000 (Walker, Rosie May) | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | © The Author(s) 2024. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-06-03T14:56:10Z | |
dc.identifier.issn | 2158-3188 | |
dc.description | This is the final version. Available on open access from Springer Nature via the DOI in this record | en_GB |
dc.description | Data availability: The terms of consent for PURE participants preclude the sharing of individual-level data. Individual level data is available through collaboration with PURE researchers (https://www.phri.ca/research/pure/). Summary-statistics for the analyses presented here are available in the supplementary materials. According to the terms of consent for GS participants, applications for individual-level data must be reviewed by the GS Access Committee (access@generationscotland.org). Complete summary statistics are available in the supplementary materials for the protein-DSST score associations assessed in this study. | en_GB |
dc.description | Code availability: The code used to generate the results in this study is available on reasonable request from the corresponding author. | en_GB |
dc.identifier.eissn | 2158-3188 | |
dc.identifier.journal | Translational Psychiatry | en_GB |
dc.relation.ispartof | Translational Psychiatry | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2024-04-23 | |
dcterms.dateSubmitted | 2023-09-20 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-04-23 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-04-23T14:03:04Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2024-06-03T14:56:15Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2024. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.