基因分析确定了与帕金森病相关脑结构有关的循环基因。

Genetic analyses identify circulating genes related to brain structures associated with Parkinson's disease.

作者信息

Han Zhe, Zhu Yanping, Xia Zhenhong, Deng Qing, He Hongjie, Yin Quanting, Zhang Hui, Yuan Mudan, Yang Chunhua, Tian Geng, Mi Jia, Xu Fuyi

机构信息

Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai, China.

School of Pharmacy, Binzhou Medical University, Yantai, China.

出版信息

NPJ Parkinsons Dis. 2025 Jan 14;11(1):17. doi: 10.1038/s41531-024-00859-z.

DOI:10.1038/s41531-024-00859-z

PMID:39809793

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11733288/

Abstract

Magnetic resonance imaging and circulating molecular testing are potential methods for diagnosing and treating Parkinson's disease (PD). However, their relationships remain insufficiently studied. Using genome-wide association summary statistics, we found in the general population a genetic negative correlation between white matter tract mean diffusivity and PD (-0.17 < Rg < -0.11, p < 0.05), and a positive correlation with intracellular volume fraction (0.12 < Rg < 0.2, p < 0.05). Additionally, 1345 circulating genes causally linked with white matter tract diffusivity were enriched for muscle physiological abnormalities (padj < 0.05). Notable genes, including LRRC37A4P (effect size = 15.7, p = 1.23E-55) and KANSL1-AS1 (effect size = -15.3, p = 1.13E-52), were directly associated with PD. Moreover, 23 genes were found linked with genetically correlated PD-IDP pairs (PPH4 > 0.8), including SH2B1 and TRIM10. Our study bridges the gap between molecular genetics, neuroimaging, and PD pathology, and suggests novel targets for diagnosis and treatment.

摘要

磁共振成像和循环分子检测是诊断和治疗帕金森病（PD）的潜在方法。然而，它们之间的关系仍未得到充分研究。利用全基因组关联汇总统计数据，我们在普通人群中发现白质束平均扩散率与PD之间存在遗传负相关（-0.17 < Rg < -0.11，p < 0.05），与细胞内体积分数呈正相关（0.12 < Rg < 0.2，p < 0.05）。此外，1345个与白质束扩散率有因果联系的循环基因在肌肉生理异常方面富集（padj < 0.05）。包括LRRC37A4P（效应大小 = 15.7，p = 1.23E-55）和KANSL1-AS1（效应大小 = -15.3，p = 1.13E-52）在内的显著基因与PD直接相关。此外，发现23个基因与遗传相关的PD-影像诊断参数对有关联（PPH4 > 0.8），包括SH2B1和TRIM10。我们的研究填补了分子遗传学、神经影像学和PD病理学之间的空白，并提出了新的诊断和治疗靶点。