Genome-wide association study of REM sleep behavior disorder in Parkinson's disease.
Sosero YL., Heilbron K., Fontanillas P., Norcliffe-Kaufmann L., Yu E., Rudakou U., Ruskey JA., Freeman K., Asayesh F., Brolin KA., Swanberg M., Morris HR., Wu L., Real R., Pihlstrøm L., Tan M., Gasser T., Brockmann K., Liu H., Hu MTM., Grosset DG., Lewis SJG., Kwok JB., Pastor P., Alvarez I., Skorvanek M., Lackova A., Ostrozovicova M., Rizig M., 23andMe Research Team ., International Parkinson’s Disease Genomics Consortium ., Krohn L., Gan-Or Z.
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.