小柯机器人

美国哈佛医学院Clemens R. Scherzer研究小组发现影响帕金森氏病认知发展的新型突触基因座。该研究于2021年5月6日在线发表于国际一流学术期刊《自然—遗传学》。

为了评估遗传变异如何影响帕金森氏病（PD）随时间推移至痴呆症（生活质量的主要决定因素），研究人员在31,053次就诊的3,821例PD患者中对1,120万个变体进行了纵向全基因组生存研究。研究人员发现RIMS2是一个进展位点，并在重复群体中证实了这一点（风险率（HR）=4.77，P=2.78×10^-11），确定了TMEM108的提示证据（HR=2.86，P=2.09×10^-8），以及WWOX（HR=2.12，P=2.37×10^-8）作为进展位点，并确认GBA（HR=1.93，P=0.0002）和APOE（HR=1.48，P=0.001）的关联。

多基因进展评分显示出与痴呆风险的实质性总体关联，而多基因易感性评分并非可预测的。这项研究确定了PD认知疾病进展的新型突触基因座和多基因评分，并提出了不同的进展和易感性的遗传结构。

据介绍，PD患者治疗和临床试验的关键驱动因素是该病随时间推移（进展和预后）的过程。

附：英文原文

Title: Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease

Author: Ganqiang Liu, Jiajie Peng, Zhixiang Liao, Joseph J. Locascio, Jean-Christophe Corvol, Frank Zhu, Xianjun Dong, Jodi Maple-Grdem, Meghan C. Campbell, Alexis Elbaz, Suzanne Lesage, Alexis Brice, Graziella Mangone, John H. Growdon, Albert Y. Hung, Michael A. Schwarzschild, Michael T. Hayes, Anne-Marie Wills, Todd M. Herrington, Bernard Ravina, Ira Shoulson, Pille Taba, Sulev Kks, Thomas G. Beach, Florence Cormier-Dequaire, Guido Alves, Ole-Bjrn Tysnes, Joel S. Perlmutter, Peter Heutink, Sami S. Amr, Jacobus J. van Hilten, Meike Kasten, Brit Mollenhauer, Claudia Trenkwalder, Christine Klein, Roger A. Barker, Caroline H. Williams-Gray, Johan Marinus, Clemens R. Scherzer

Issue&Volume: 2021-05-06

Abstract: A key driver of patients’ well-being and clinical trials for Parkinson’s disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR)=4.77, P=2.78×1011), identify suggestive evidence for TMEM108 (HR=2.86, P=2.09×108) and WWOX (HR=2.12, P=2.37×108) as progression loci, and confirm associations for GBA (HR=1.93, P=0.0002) and APOE (HR=1.48, P=0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.

DOI: 10.1038/s41588-021-00847-6

Source: https://www.nature.com/articles/s41588-021-00847-6

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex