A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1

Helene Catoire, Faezeh Sarayloo, Karim Mourabit Amari, Sergio Apuzzo, Alanna Grant, Daniel Rochefort, Lan Xiong, Jacques Montplaisir, Christopher J Earley, Gustavo Turecki, Patrick A. Dion, Guy A. Rouleau

Research output: Contribution to journalArticle

Abstract

Restless Legs syndrome (RLS) is a common sleep disorder for which the genetic contribution remains poorly explained. In 2007, the first large scale genome wide association study (GWAS) identified three genomic regions associated with RLS. MEIS1, BTBD9 and MAP2K5/SKOR1 are the only known genes located within these loci and their association with RLS was subsequently confirmed in a number of follow up GWAS. Following this finding, our group reported the MEIS1 risk haplotype to be associated with its decreased expression at the mRNA and protein levels. Here we report the effect of the risk variants of the three other genes strongly associated with RLS. While these variants had no effect on the mRNA levels of the genes harboring them, we find that the homeobox transcription factor MEIS1 positively regulates the expression of the transcription co-repressor SKOR1. This regulation appears mediated through the binding of MEIS1 at two specific sites located in the SKOR1 promoter region and is modified by an RLS associated SNP in the promoter region of the gene. Our findings directly link MEIS1 and SKOR1, two significantly associated genes with RLS and also prioritize SKOR1 over MAP2K5 in the RLS associated intergenic region of MAP2K5/SKOR1 found by GWAS.

Original languageEnglish (US)
Article number12173
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Restless Legs Syndrome
Genome-Wide Association Study
Genes
Genetic Promoter Regions
Co-Repressor Proteins
Messenger RNA
Intergenic DNA
Homeobox Genes
Haplotypes
Single Nucleotide Polymorphism
Transcription Factors

ASJC Scopus subject areas

  • General

Cite this

Catoire, H., Sarayloo, F., Mourabit Amari, K., Apuzzo, S., Grant, A., Rochefort, D., ... Rouleau, G. A. (2018). A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1. Scientific Reports, 8(1), [12173]. https://doi.org/10.1038/s41598-018-30665-6

A direct interaction between two Restless Legs Syndrome predisposing genes : MEIS1 and SKOR1. / Catoire, Helene; Sarayloo, Faezeh; Mourabit Amari, Karim; Apuzzo, Sergio; Grant, Alanna; Rochefort, Daniel; Xiong, Lan; Montplaisir, Jacques; Earley, Christopher J; Turecki, Gustavo; Dion, Patrick A.; Rouleau, Guy A.

In: Scientific Reports, Vol. 8, No. 1, 12173, 01.12.2018.

Research output: Contribution to journalArticle

Catoire, H, Sarayloo, F, Mourabit Amari, K, Apuzzo, S, Grant, A, Rochefort, D, Xiong, L, Montplaisir, J, Earley, CJ, Turecki, G, Dion, PA & Rouleau, GA 2018, 'A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1', Scientific Reports, vol. 8, no. 1, 12173. https://doi.org/10.1038/s41598-018-30665-6
Catoire H, Sarayloo F, Mourabit Amari K, Apuzzo S, Grant A, Rochefort D et al. A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1. Scientific Reports. 2018 Dec 1;8(1). 12173. https://doi.org/10.1038/s41598-018-30665-6
Catoire, Helene ; Sarayloo, Faezeh ; Mourabit Amari, Karim ; Apuzzo, Sergio ; Grant, Alanna ; Rochefort, Daniel ; Xiong, Lan ; Montplaisir, Jacques ; Earley, Christopher J ; Turecki, Gustavo ; Dion, Patrick A. ; Rouleau, Guy A. / A direct interaction between two Restless Legs Syndrome predisposing genes : MEIS1 and SKOR1. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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