Laboratorio Internacional de Investigación Sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México.
Mental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
J Parkinsons Dis. 2024;14(3):483-493. doi: 10.3233/JPD-230176.
Depression is a common symptom in Parkinson's disease (PD), resulting from underlying neuropathological processes and psychological factors. However, the extent to which shared genetic risk factors contribute to the relationship between depression and PD is poorly understood.
To examine the effects of common genetic variants influencing the etiology of PD and depression risk at the genome-wide and local genomic regional level.
We comprehensively investigated the genetic relationship between PD and depression using genome-wide association studies data. First, we estimated the genetic correlation at the genome-wide level using linkage-disequilibrium score regression, followed by local genetic correlation analysis using the GWAS-pairwise method and functional annotation to identify genes that may jointly influence the risk for both traits. Also, we performed Latent Causal Variable, Latent Heritable Confounder Mendelian Randomization, and traditional Mendelian Randomization analyses to investigate the potential causal relationship.
Although the genetic correlation between PD and depression was not statistically significant at the genome-wide level, GWAS-pairwise analyses identified 16 genomic segments associated with PD and depression, implicating nine genes. Further analyses revealed distinct patterns within individual genes, suggesting an intricate pattern. These genes involve various biological processes, including neurotransmitter regulation, senescence, and nucleo-cytoplasmic transport mechanisms. We did not observe genetic evidence of causality between PD and depression.
Our findings did not support a genome-wide genetic correlation or a causal association between both conditions. However, we identified genomic segments but identified genomic segments linked to distinct biological pathways influencing their etiology.Further research is needed to understand their functional consequences.
抑郁症是帕金森病（PD）的常见症状，其发病机制源于潜在的神经病理学过程和心理因素。然而，共同的遗传风险因素在多大程度上导致了抑郁与 PD 之间的关系尚不清楚。
在全基因组和局部基因组区域水平上，检查影响 PD 和抑郁风险的常见遗传变异的影响。
我们使用全基因组关联研究数据全面研究了 PD 和抑郁之间的遗传关系。首先，我们使用连锁不平衡评分回归在全基因组水平上估计遗传相关性，然后使用 GWAS-成对方法和功能注释进行局部遗传相关性分析，以识别可能共同影响两种特征风险的基因。此外，我们还进行了潜在因果变量、潜在遗传性混杂因素孟德尔随机化和传统孟德尔随机化分析，以调查潜在的因果关系。
虽然 PD 和抑郁之间的遗传相关性在全基因组水平上没有统计学意义，但 GWAS-成对分析确定了 16 个与 PD 和抑郁相关的基因组片段，涉及 9 个基因。进一步的分析显示了个别基因内的不同模式，表明存在复杂的模式。这些基因涉及各种生物学过程，包括神经递质调节、衰老和核质转运机制。我们没有观察到 PD 和抑郁之间存在遗传因果关系的证据。
我们的研究结果不支持这两种情况之间存在全基因组遗传相关性或因果关系。然而，我们确定了与不同生物学途径相关的基因组片段，这些途径影响其发病机制。需要进一步的研究来了解它们的功能后果。
