SMPD1 variants do not have a major role in REM sleep behavior disorder

Abstract

Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). The majority of patients with isolated rapid eye movement sleep behavior disorder (iRBD) develop PD or DLB later in life, suggesting that iRBD is a prodromal phase of these two conditions. In the current study we aimed to evaluate the role of SMPD1 variants in iRBD. SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1,287 controls from European descent. Logistic regression adjusted for sex and age showed no significant associations with two common variants and iRBD (rs1050239 and rs8164). The frequency of all rare nonsynonymous SMPD1 variants (minor allele frequency <1%) was found to be twice as high in cases than in controls (1.46% vs. 0.70%, Fisher's exact test p=0.09) but there was no statistically significant burden (p=0.64). Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.