帕金森病的LRRK2罕见变异单结构域遗传负担：局限于激酶结构域的关联

IF 6.7 1区医学 Q1 NEUROSCIENCES

NPJ Parkinson's Disease Pub Date : 2025-04-29 DOI:10.1038/s41531-025-00934-z

Sitki Cem Parlar, Konstantin Senkevich, Eric Yu, Jennifer A. Ruskey, Jamil Ahmad, Farnaz Asayesh, Dan Spiegelman, Cheryl Waters, Oury Monchi, Yves Dauvilliers, Nicolas Dupré, Lior Greenbaum, Sharon Hassin-Baer, Irina Miliukhina, Alla Timofeeva, Anton Emelyanov, Sofya Pchelina, Roy N. Alcalay, Edward A. Fon, Jean-François Trempe, Ziv Gan-Or

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引用次数: 0

摘要

LRRK2变异是帕金森病（PD）的关键遗传危险因素。我们进行了每域罕见编码变异负担分析，包括8888例PD病例和69412例对照。在荟萃分析中，激酶结构域与PD密切相关（外显子：PFDR = 1.61 × 10−22，非同义：PFDR = 1.54 × 10−23,CADD > 20: PFDR = 3.09 × 10−24）。排除p.G2019S变体使这种影响无效。在ANK和Roc-COR域中发现了名义上的关联，具有潜在的保护性变异，p.R793M和p.r 1353k。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

LRRK2 rare-variant per-domain genetic burden in Parkinson’s Disease: association confined to the kinase domain

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LRRK2 rare-variant per-domain genetic burden in Parkinson’s Disease: association confined to the kinase domain

LRRK2 variants are key genetic risk factors for Parkinson’s Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: P^FDR = 1.61 × 10⁻²², Non-synonymous: P^FDR = 1.54 × 10⁻²³, CADD > 20: P^FDR = 3.09 × 10⁻²⁴). Excluding the p.G2019S variant nullified this effect. Nominal associations were found in the ANK and Roc-COR domains, with potentially protective variants, p.R793M and p.Q1353K.

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来源期刊

NPJ Parkinson's Disease Medicine-Neurology (clinical)

CiteScore

9.80

自引率

5.70%

发文量

156

审稿时长

11 weeks

期刊介绍： npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.