Genome-wide association study of REM sleep behavior disorder in Parkinson’s disease

作者：Yuri L. Sosero, Karl Heilbron, Pierre Fontanillas, Lucy Norcliffe‐Kaufmann, Eric Yu, Uladzislau Rudakou, Jennifer A. Ruskey, Kathryn Freeman, Farnaz Asayesh, Kajsa 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 Pástor, Ignacio Álvarez, Matěj Škorvánek, Alexandra Lacková, Miriam Ostrožovičová, Mie Rizig, Lynne Krohn, Ziv Gan‐Or · 发表于：npj Parkinson s Disease · 年份：2025 · DOI：10.1038/s41531-025-01078-w · 被引用次数：3 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Autism Spectrum Disorder Research

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.