| Title: | Measurement characteristics and genome-wide correlates of lifetime brain atrophy estimated from a single MRI |
| Journal: | Nature Communications |
| Published: | 21 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40691153/ |
| DOI: | https://doi.org/10.1038/s41467-025-61978-6 |
Publication 16134
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
As a cardinal marker of brain ageing, lifetime brain atrophy obtained from a cross-sectional magnetic resonance image promises to boost statistical power to uncover novel genetic mechanisms of neurodegeneration. By analysing five young and old adult cohorts, we perform the most definitive study on lifetime brain atrophy's measurement and correlates. It is simply calculated from the relationship between total brain volume and intracranial volume, using the difference, ratio, or regression-residual method. Lifetime brain atrophy is correlated with well-validated neuroradiological atrophy ratings (r = 0.37-0.44), cognitive decline (r = 0.36), frailty (r = 0.24), and longitudinally-measured atrophic changes (r = 0.36). Lifetime brain atrophy computed with the difference method yields phenotypic and genetic signal similar to baseline intracranial volume (rg = 0.75), in contrast to the residual method, which also best captures brain shrinkage. Lifetime brain atrophy is highly heritable (h2SNP = 41%[95%CI = 38-43%]), and the strongest genome-wide association (N = 43,110) implicates WNT16, a gene linked with neurodegenerative diseases.</p>
17 Keywords
- Adult
- Aged
- Aged, 80 and over
- Aging
- Atrophy
- Brain
- Cognitive Dysfunction
- Cross-Sectional Studies
- Female
- Genome-Wide Association Study
- Humans
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Neurodegenerative Diseases
- Organ Size
- Young Adult
24 Authors
- Anna E. Fürtjes
- Isabelle F. Foote
- Charley Xia
- Gail Davies
- Joanna Moodie
- Adele Taylor
- David C. Liewald
- Paul Redmond
- Janie Corley
- Andrew M. McIntosh
- Heather C. Whalley
- Susana Muñoz Maniega
- Maria Valdés Hernández
- Ellen Backhouse
- Karen Ferguson
- Mark E. Bastin
- Joanna Wardlaw
- Javier de la Fuente
- Andrew D. Grotzinger
- Michelle Luciano
- W. David Hill
- Ian J. Deary
- Elliot M. Tucker-Drob
- Simon R. Cox
1 Application
| Application ID | Title |
|---|---|
| 10279 | The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
Enabling scientific discoveries that improve human health