Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Mov Disord. 2021 Feb;36(2):434-441. doi: 10.1002/mds.28353. Epub 2020 Nov 5.
Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease.
We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease.
Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10 ).
We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.
帕金森病是第二大常见的神经退行性疾病，影响所有种族背景的人，但对非欧洲人群帕金森病的遗传学知之甚少。此外，在帕金森病患者中，全基因组范围内拷贝数变异的整体鉴定研究还很少。本研究的目的是了解拉丁裔人群全基因组拷贝数变异的负担及其与帕金森病的关系。
我们使用来自拉丁美洲帕金森病遗传学研究联盟的 747 名帕金森病患者和 632 名对照的全基因组基因分型数据。
全基因组拷贝数负担分析显示，与对照组相比，患者中与已知帕金森病基因重叠的拷贝数变异明显富集（优势比，3.97；95%CI，1.69-10.5；P = 0.018）。PRKN 显示出最强的拷贝数负担，有 20 个拷贝数变异携带者。与其他拷贝数变异的患者相比，这些患者的发病年龄更早（发病中位年龄，分别为 31 岁和 57 岁；P = 7.46×10）。
我们发现，尽管全基因组拷贝数变异负担总体上没有显著差异，但帕金森病患者中已知帕金森病基因受影响的拷贝数变异明显富集。我们还发现，在我们的队列中，250 名早发性疾病患者中有 5.6%携带 PRKN 的拷贝数变异。本研究首次分析了拉丁裔帕金森病患者的全基因组拷贝数变异相关性，并为这一复杂疾病在这一研究较少的人群中提供了新的见解。© 2020 国际帕金森病和运动障碍协会。
