School of Medicine Publications and Presentations
The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease
Document Type
Article
Publication Date
3-27-2024
Abstract
We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.
Recommended Citation
Manuello, J., Min, J., McCarthy, P., Alfaro-Almagro, F., Lee, S., Smith, S., ... & Douaud, G. (2024). The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease. Nature Communications, 15(1), 2576. https://doi.org/10.1038/s41467-024-46344-2
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Nature Communications
DOI
10.1038/s41467-024-46344-2
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
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.