分析4万多人脑影像数据，发现男女脑衰老的基因机制不同
Genetic Influences on Brain Aging: Analyzing Sex Differences in the UK Biobank using Structural MRI
- 分性别做全基因组关联分析，找与脑衰老相关的基因
- 女性多涉及神经递质和线粒体应激基因，男性则与免疫炎症相关
- 发现共有的核心基因，适合研究个性化抗衰老干预
男女脑衰老轨迹存在差异，但背后的遗传因素仍不清楚。基于40,940名英国生物银行参与者（年龄45-83岁）的结构磁共振成像与基因型数据，我们计算了全脑、海马和脑室体积的脑年龄差距估计值（BrainAGE）。通过分性别的全基因组关联研究（GWAS）及后续分析，识别出与加速脑衰老相关的遗传变异。女性中显著富集于神经递质转运和线粒体应激反应基因；男性则以免疫与炎症相关基因为主。共有基因如GMNC和OSTN在两性中均与脑体积相关，提示其在神经结构维持中的核心作用。组织表达分析显示，与神经退行性病变相关的通路存在性别特异性富集。研究强调了在衰老研究中采用分性别方法的重要性，并为个体化抗认知衰退干预提供了遗传靶点。
原文摘要 · Abstract (English)
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.
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