Integrated genetic analysis and single cell-RNA sequencing for brain image-derived phenotypes and Parkinson's disease

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-03-11 DOI:10.1016/j.pnpbp.2025.111317

Lin Pan , Laiyu Yang , Weijie Ding , Yongfei Hu , Wenzhuo Yang , Jingning Wang , Zhiyun Zhang , Kangli Fan , Zhihui Sun , Yue Liang , Xiaoyue Lin , Jun Chen , Ying Zhang

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引用次数: 0

Abstract

Background

Previous studies have reported Parkinson's disease (PD) patients usually have changes in brain image-derived phenotypes (IDPs). However, the role of genetic factors in their association and biological mechanism remains unclear. We aimed to unveil genetic and biological links between brain IDPs and PD.

Methods

Using genome-wide association study (GWAS) summary statistics and single-cell RNA sequencing (scRNA-seq) data, we performed a comprehensive analysis between 624 brain IDPs and PD. The genetic correlations and causality were examined by linkage disequilibrium score regression (LDSC), two-sample bidirectional Mendelian randomization (MR) and meta-analysis. Potential shared genes were identified using MAGMA and PLACO. Finally, pathway enrichment using FUMA and Metascape, and scRNA-seq analysis were performed to determine biological mechanisms and gene expression atlas across various cell types in brain tissue.

Results

LDSC revealed that 50 brain IDPs were genetically correlated with PD (P < 0.05), in which 5 IDPs, exhibited putative causality on PD through MR (P < 0.05). For instance, we identified that the increased volume of the right thalamus (IVW: OR = 2.08, 95 % CI: 1.33 to 3.25, PFDR = 0.03) was positively correlated with the risk of PD, which was also supported by replicated MR (IVW: OR = 1.63, 95 % CI: 1.17–2.26, PFDR = 0.02) in FinnGen and meta-analysis (OR = 1.78, 95 % CI: 1.36–2.31, PFDR = 5.00 × 10⁻⁴). Additionally, we identified 56 unique pleiotropic genes, such as FAM13A, with notable enrichment in neuronal cells. Biological mechanism analysis revealed these genes were enriched in brain tissues and a variety of pathways such as negative regulation of neuron apoptotic processes.

Conclusion

We indicated the shared genetic architecture and biological mechanisms between brain IDPs and PD. These findings might provide insights on the therapeutic intervention and early prediction of PD at the brain imaging level.

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针对脑图像衍生表型和帕金森病的综合基因分析和单细胞-RNA 测序

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.