大脑皮层的形态变化和基因表达水平因果关系地影响了对2型糖尿病的易感性:孟德尔的随机化研究
Fanghang Ye1, Yucheng Huang2, Na Li1
1Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Experimental gerontology
|May 21, 2025
概括
大脑皮层结构影响2型糖尿病 (T2D) 风险,特定区域如Pars Opercularis和Supramarginal gyrus与增加T2D易感性有关. 基因表达也在T2D发育中起作用.
科学领域:
- 神经遗传学 神经遗传学
- 代谢障碍 代谢障碍 代谢障碍
- 大脑与身体的相互作用
背景情况:
- 对2型糖尿病 (T2D) 与神经/精神疾病之间的联系越来越感兴趣.
- 之前的研究表明大脑皮层与这些疾病之间存在相关性.
- 大脑皮层特征与T2D风险之间的因果关系尚不清楚.
研究的目的:
- 使用孟德尔随机化研究大脑皮层结构和功能在2型糖尿病 (T2D) 风险中的因果关系.
- 为了确定特定的基因和大脑中的途径,有助于T2D易感性.
- 探索T2D和其他疾病表型之间的共同遗传基础.
主要方法:
- 系统的门德尔随机化 (MR) 研究,利用全基因组关联研究 (GWAS) 和表达量化特征位置 (eQTL) 数据.
- 脑皮层表面积 (SA) 和厚度 (TH) 与T2D风险相关的分析.
- 使用了基于总结数据的MR (SMR),局部化,调解MR和全现象关联研究 (PheWAS).
主要成果:
- 特定的大脑皮层特征,包括Pars Opercularis SA和Supramarginal gyrus TH,与增加T2D风险有关.
- 前中心皮层等区域的加厚和前中心区域的SA减少与T2D风险的降低有关.
- 三个基因 (NUDC,PACC1,RAB29) 被确定为对T2D易感性的因果影响,NUDC显示脑特异性表达,RAB29通过皮质SA和TH介导作用.
结论:
- 中枢神经系统在对2型糖尿病 (T2D) 的遗传倾向中发挥着重要作用.
- 鉴定出基因和大脑区域为T2D背后的机制提供了新的见解.
- 研究结果表明,T2D,神经系统疾病,心血管疾病和恶性瘤之间存在共同的遗传途径.
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