Genetic Influences on Brain Aging: Analyzing Sex Differences in the UK Biobank using Structural MRI
Fuente:
arXiv
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Preprint |
| Published: |
2025
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1866910970950975488 |
|---|---|
| author | Ardila, Karen Mohite, Aashka Addeh, Abdoljalil Tyndall, Amanda V. Barha, Cindy K. Long, Quan MacDonald, M. Ethan |
| author_facet | Ardila, Karen Mohite, Aashka Addeh, Abdoljalil Tyndall, Amanda V. Barha, Cindy K. Long, Quan MacDonald, M. Ethan |
| contents | Brain aging trajectories differ between males and females, yet the genetic factors underlying these differences remain underexplored. Using structural MRI and genotyping data from 40,940 UK Biobank participants (aged 45-83), we computed Brain Age Gap Estimates (BrainAGE) for total brain, hippocampal, and ventricular volumes. We conducted sex-stratified genome-wide association studies (GWAS) and Post-GWAS analyses to identify genetic variants associated with accelerated brain aging. Distinct gene sets emerged by sex: in females, neurotransmitter transport and mitochondrial stress response genes were implicated; in males, immune and inflammation-related genes dominated. Shared genes, including GMNC and OSTN, were consistently linked to brain volumes across sexes, suggesting core roles in neurostructural maintenance. Tissue expression analyses revealed sex-specific enrichment in pathways tied to neurodegeneration. These findings highlight the importance of sex-stratified approaches in aging research and suggest genetic targets for personalized interventions against age-related cognitive decline. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2505_20344 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Genetic Influences on Brain Aging: Analyzing Sex Differences in the UK Biobank using Structural MRI Ardila, Karen Mohite, Aashka Addeh, Abdoljalil Tyndall, Amanda V. Barha, Cindy K. Long, Quan MacDonald, M. Ethan Genomics Machine Learning Brain aging trajectories differ between males and females, yet the genetic factors underlying these differences remain underexplored. Using structural MRI and genotyping data from 40,940 UK Biobank participants (aged 45-83), we computed Brain Age Gap Estimates (BrainAGE) for total brain, hippocampal, and ventricular volumes. We conducted sex-stratified genome-wide association studies (GWAS) and Post-GWAS analyses to identify genetic variants associated with accelerated brain aging. Distinct gene sets emerged by sex: in females, neurotransmitter transport and mitochondrial stress response genes were implicated; in males, immune and inflammation-related genes dominated. Shared genes, including GMNC and OSTN, were consistently linked to brain volumes across sexes, suggesting core roles in neurostructural maintenance. Tissue expression analyses revealed sex-specific enrichment in pathways tied to neurodegeneration. These findings highlight the importance of sex-stratified approaches in aging research and suggest genetic targets for personalized interventions against age-related cognitive decline. |
| title | Genetic Influences on Brain Aging: Analyzing Sex Differences in the UK Biobank using Structural MRI |
| topic | Genomics Machine Learning |
| url | https://arxiv.org/abs/2505.20344 |