Yuri L Sosero, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe-Kaufmann, Eric Yu, Uladzislau Rudakou, Jennifer A Ruskey, Kathryn Freeman, Farnaz Asayesh, Kajsa A Brolin, Maria Swanberg, Huw R Morris, Lesley Wu, Raquel Real, Lasse Pihlstrøm, Manuela Tan, Thomas Gasser, Kathrin Brockmann, Hui Liu, Michele T M Hu, Donald G Grosset, Simon J G Lewis, John B Kwok, Pau Pastor, Ignacio Alvarez, Matej Skorvanek, Alexandra Lackova, Miriam Ostrozovicova, Mie Rizig, Lynne Krohn, Ziv Gan-Or
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引用次数: 0
摘要
快速眼动睡眠行为障碍（RBD）是一种影响帕金森病（PD）患者亚群的前驱突触核蛋白病，与神经精神症状相关。本研究使用全基因组关联研究（GWAS）比较了13020例PD + RBD患者和5403例无PD-RBD患者的遗传谱。RBD通过问卷调查或自我报告进行评估。神经精神特征与PD + RBD之间的潜在遗传相关性采用连锁不平衡评分回归进行评估。SNCA位点的顶端变异与PD + RBD相关（rs10005233-T, OR = 1.21, 95% CI = 1.16-1.27, p = 1.81e-15）。SNCA的PD危险变异（rs5019538-G, OR = 0.85, 95% CI = 0.81-0.89, p = 2.46e-10; rs356182-G, OR = 0.89, 95% CI = 0.84-0.95, p = 0.0001）和LRRK2基因座（rs34637584, OR = 0.41, 95% CI = 0.28-0.61, p = 1.04e-5）与PD + RBD风险降低相关。注意缺陷多动障碍与PD + RBD之间存在提示性的遗传相关性，但校正后无统计学意义。这些发现强调了PD + RBD和PD-RBD之间的遗传差异，为PD分层和潜在的亚型特异性治疗提供了见解。
Genome-wide association study of REM sleep behavior disorder in Parkinson's disease.
REM sleep behavior disorder (RBD), is a prodromal synucleinopathy affecting a subset of Parkinson's disease (PD) patients and associated with neuropsychiatric symptoms. This study compared the genetic profiles of 13,020 PD patients with probable RBD (PD + RBD) and 5403 without (PD-RBD) using genome-wide association study (GWAS). RBD was assessed by questionnaires or self-reporting. Potential genetic correlations between neuropsychiatric traits and PD + RBD were assessed using linkage disequilibrium score regression. The top variant in the SNCA locus was associated with PD + RBD (rs10005233-T, OR = 1.21, 95% CI = 1.16-1.27, p = 1.81e-15). PD risk variants in SNCA (rs5019538-G, OR = 0.85, 95% CI = 0.81-0.89, p = 2.46e-10; rs356182-G, OR = 0.89, 95% CI = 0.84-0.95, p = 0.0001) and LRRK2 loci (rs34637584, OR = 0.41, 95% CI = 0.28-0.61, p = 1.04e-5) were associated with reduced PD + RBD risk. A suggestive genetic correlation between attention deficit hyperactivity disorder and PD + RBD was observed but was not statistically significant after correction. These findings highlight genetic distinctions between PD + RBD and PD-RBD, offering insights into PD stratification and potential subtype-specific treatments.
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.
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