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[Preprint]. 2023 Nov 9:2023.11.07.23298092.
doi: 10.1101/2023.11.07.23298092.

The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians

Oluwadamilola O Ojo  1   2 , Sara Bandres-Ciga  3 , Mary B Makarious  4   5 , Peter Wild Crea  4   5 , Dena G Hernandez  4 , Henry Houlden  6 , Mie Rizig  6 , Andrew B Singleton  3   4 , Alastair J Noyce  7 , Mike A Nalls  3   4   8 , Cornelis Blauwendraat  3   4 , Njideka U Okubadejo  1   2
Affiliations

The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians

Oluwadamilola O Ojo et al. medRxiv. .

Update in

Abstract

Background: Damaging coding variants in GBA1 are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies. Recently, a population-specific non-coding variant (rs3115534) was found to be associated with PD risk and earlier disease onset in individuals of African ancestry.

Objectives: To investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD.

Methods: We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. The GBA1 rs3115534 risk variant status was imputed from previous genotyping for all. Symptoms of RBD were assessed with the RBD screening questionnaire (RBDSQ).

Results: The non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (Beta = 0.3640, SE = 0.103, P =4.093e-04), as well as after adjusting for PD status (Beta = 0.2542, SE = 0.108, P = 0.019) suggesting that this variant may have the same downstream consequences as GBA1 coding variants.

Conclusions: We show that the non-coding GBA1 rs3115534 risk variant is associated with increased RBD symptomatology in Nigerians with PD. Further research is required to assess association with polysomnography-defined RBD.

Keywords: GBA1; Genetics; Nigeria; Nigerians; Parkinson’s disease; RBD; REM parasomnia; REM sleep behavior disorder; rs3115534; sub-Saharan Africa.

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Conflict of interest statement

M.A.N.’s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board at Clover Therapeutics and is an advisor and scientific founder at Neuron23 Inc.

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