TY - JOUR
T1 - TOX3 Variants Are Involved in Restless Legs Syndrome and Parkinson’s Disease with Opposite Effects
AU - Mohtashami, Sadaf
AU - He, Qin
AU - Ruskey, Jennifer A.
AU - Zhou, Sirui
AU - Dion, Patrick A.
AU - Allen, Richard P.
AU - Earley, Christopher J.
AU - Fon, Edward A.
AU - Xiong, Lan
AU - Dupre, Nicolas
AU - Dauvilliers, Yves
AU - Rouleau, Guy A.
AU - Gan-Or, Ziv
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Parkinson’s disease (PD) and restless legs syndrome (RLS) may be clinically and/or etiologically related, yet this association is under debate. Single-nucleotide polymorphisms (SNPs) in the TOX3 gene locus were implicated in both RLS and PD genome-wide association studies (GWASs), suggesting a potential pleiotropy. Two case-control cohorts including 644 PD patients, 457 RLS patients, and 945 controls were genotyped for one known RLS-related SNP (rs3104767) and one PD-related SNP (rs4784226) in the TOX3 locus. The associations between genotype and PD and RLS risk were tested using multivariate regression models. The allele frequencies of RLS-related SNP rs3104767 in RLS patients and controls were 0.35 and 0.43, respectively (OR 0.70, p = 0.0007). Regression model suggested that this association is derived by homozygous carriage of rs3104767 (adjusted p = 0.008). A nominal association was observed for homozygous carriers of the rs3104767 SNP in PD (OR 1.62, 95% CI 1.05–2.54, p = 0.034), i.e., with an opposite direction of effect on RLS and PD, but this was not significant after Bonferroni correction. However, data from published GWASs of RLS and PD, and from the PDgene database, further supported these inverse associations. Our results confirm the association between the TOX3 SNP rs3104767 and RLS and suggest that TOX3 variants are involved in both RLS and PD, but with different or even opposite effects. Studies in larger populations of different ethnicities are required to further refine the TOX3 locus is involved in RLS and PD.
AB - Parkinson’s disease (PD) and restless legs syndrome (RLS) may be clinically and/or etiologically related, yet this association is under debate. Single-nucleotide polymorphisms (SNPs) in the TOX3 gene locus were implicated in both RLS and PD genome-wide association studies (GWASs), suggesting a potential pleiotropy. Two case-control cohorts including 644 PD patients, 457 RLS patients, and 945 controls were genotyped for one known RLS-related SNP (rs3104767) and one PD-related SNP (rs4784226) in the TOX3 locus. The associations between genotype and PD and RLS risk were tested using multivariate regression models. The allele frequencies of RLS-related SNP rs3104767 in RLS patients and controls were 0.35 and 0.43, respectively (OR 0.70, p = 0.0007). Regression model suggested that this association is derived by homozygous carriage of rs3104767 (adjusted p = 0.008). A nominal association was observed for homozygous carriers of the rs3104767 SNP in PD (OR 1.62, 95% CI 1.05–2.54, p = 0.034), i.e., with an opposite direction of effect on RLS and PD, but this was not significant after Bonferroni correction. However, data from published GWASs of RLS and PD, and from the PDgene database, further supported these inverse associations. Our results confirm the association between the TOX3 SNP rs3104767 and RLS and suggest that TOX3 variants are involved in both RLS and PD, but with different or even opposite effects. Studies in larger populations of different ethnicities are required to further refine the TOX3 locus is involved in RLS and PD.
KW - Genetics
KW - Parkinson’s disease
KW - Restless legs syndrome
KW - TOX3
UR - http://www.scopus.com/inward/record.url?scp=85044622370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044622370&partnerID=8YFLogxK
U2 - 10.1007/s12031-018-1031-4
DO - 10.1007/s12031-018-1031-4
M3 - Article
C2 - 29404899
AN - SCOPUS:85044622370
SN - 0895-8696
VL - 64
SP - 341
EP - 345
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -