Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.
Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.
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拉丁美洲帕金森病患者拷贝数变异的全基因组分析。
DOI：
10.1002/mds.28353
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡
中科院分区：
文献类型：
--
作者：
Sarihan EI;Pérez-Palma E;Niestroj LM;Loesch D;Inca-Martinez M;Horimoto ARVR;Cornejo-Olivas M;Torres L;Mazzetti P;Cosentino C;Sarapura-Castro E;Rivera-Valdivia A;Dieguez E;Raggio V;Lescano A;Tumas V;Borges V;Ferraz HB;Rieder CR;Schumacher-Schuh AF;Santos-Lobato BL;Velez-Pardo C;Jimenez-Del-Rio M;Lopera F;Moreno S;Chana-Cuevas P;Fernandez W;Arboleda G;Arboleda H;Arboleda-Bustos CE;Yearout D;Zabetian CP;Thornton TA;O'Connor TD;Lal D;Mata IF;Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡
帕金森病是第二种最常见的神经退行性疾病，影响所有种族背景的人，但对非欧洲人群中帕金森病的遗传学知之甚少。此外，在全基因组水平上对拷贝数变异的总体识别在帕金森病患者中研究不足。本研究的目的是了解拉丁美洲人拷贝数变异的全基因组负担及其与帕金森病的关系。我们使用了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。全基因组拷贝数负荷分析显示，与对照组相比，患者明显富集了与已知帕金森病基因重叠的拷贝数变异（优势比，3.97; 95%CI，1.69-10.5; P = 0.018）。PRKN表现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（发病时的中位年龄分别为31岁和57岁; P = 7.46 × 10−7）。我们发现，虽然整体基因组范围内的拷贝数变异负担没有显着差异，帕金森病患者显着丰富的拷贝数变异影响已知的帕金森病基因。我们还发现，在我们的队列中，250例早发性疾病患者中有5.6%携带PRKN拷贝数变异。我们的研究是第一个分析拉丁裔帕金森病患者全基因组拷贝数变异相关性的研究，并为这一研究不足的人群提供了关于这一复杂疾病的见解。
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 × 10−7). 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.
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