The bidirectional causal effects of brain morphology across the life course and risk of Alzheimers disease: A cross-cohort comparison and Mendelian randomization meta-analysis
By
Roxanna Korologou-Linden,
Bing Xu,
Elizabeth Coulthard,
Esther Walton,
Alfie Wearn,
Gibran Hemani,
Tonya JH White,
Charlotte A.M. Cecil,
Tamsin Sharp,
Lorenza Dall'Aglio,
Tobias Banaschewski,
Arun Bokde,
Erin Quinlan,
Sylvane Desrivieres,
Herta Flor,
Antoine Grigis,
Penny Gowland,
Andreas Heinz,
Rudiger Bruhl,
Jean-Luc Martinot,
Marie-Laure Paillere Martinot,
Eric Artiges,
Frauke Nees,
Dimitris Papadopoulos Orfanos,
Tomas Paus,
Luise Poustka,
Millenet Sabina,
Juliane Frohner,
Lauren Robinson,
Michael Smolka,
Henrik Walter,
Jeanne Winterer,
Robert Whelan,
Gunter Schumann,
Laura D Howe,
Yoav Ben-Shlomo,
Neil M Davies,
Emma L Anderson
Posted 18 May 2021
medRxiv DOI: 10.1101/2021.05.14.21256707
Neuropathological changes associated with Alzheimers disease (AD) can occur decades before clinical symptoms. We investigated whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or accelerating brain atrophy, respectively. We used bidirectional two-sample Mendelian randomization to estimate the effects of genetic liability to AD on global and regional cortical thickness, total intracranial volume, volume of subcortical structures and cerebral white matter in 36,842 participants aged eight to 81 years across five independent cohorts, and the effects of global and regional cortical thickness and subcortical volumes on AD risk in 94,337 participants. Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. We also found little evidence to suggest brain morphology alters AD risk. Thus, genetic liability to AD is likely to alter mechanisms and/or rates of neurodegeneration, rather than reduce structural brain reserve.
Download data
- Downloaded 463 times
- Download rankings, all-time:
- Site-wide: 113,414
- In genetic and genomic medicine: 746
- Year to date:
- Site-wide: 161,413
- Since beginning of last month:
- Site-wide: 87,346
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!