Genetic reports abstractAssociation study of essential tremor genetic loci in Parkinson's disease
Introduction
Parkinson's disease (PD) and essential tremor (ET) are common movement disorders that affect a significant proportion of the elderly population. ET generally presents as an action tremor without neurodegeneration, whereas PD presents as a resting tremor, along with other motor and nonmotor symptoms. Interestingly, several studies suggested an overlap between ET and PD risk. The risk to develop PD after an initial diagnosis of ET was 4-fold when compared to a non-ET population (Algarni and Fasano, 2017), and individuals with a PD-diagnosed relative are more likely (depending on age and gender) to develop ET (Rocca et al., 2007). While the 2 diseases are mostly distinct in their etiology and symptoms, there may be potential genetic pleiotropy between the diseases (Rocca et al., 2007). A recent genome-wide association study (GWAS) has suggested associations between several loci and ET (Muller et al., 2016). Because the clinical and genetic link between PD and ET are still not fully understood, we screened variants from the recent ET GWAS (Muller et al., 2016) in a cohort of French and French-Canadian PD patients and unaffected controls. See Supplementary Material for detailed introduction and full list of references.
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Samples
A case-control series consisting of 717 subjects with PD (average age 65.94 ± 9.42 years, 1.79 male-female ratio) and 595 unrelated, unaffected controls (51.68 ± 13.14 years, 1.11 male-female ratio) was included in this study. Details on recruitment and detailed methods can be found in the Supplementary Material. All subjects provided informed consent, and the study was approved by the respective institutional review boards.
Variant selection
The top 22 single-nucleotide polymorphisms (SNPs) most significantly
Results
A total of 56 samples (0.036) were excluded from subsequent analysis as they had genotyping call rates <0.90. Hence, a total of 679 PD patients and 577 controls were included in the regression model, and the final genotyping call rate across all samples was 0.995. No variants significantly deviated from Hardy-Weinberg equilibrium (all had p > 0.01). Table 1 details the association of the ET SNPs with PD in our cohort. Following multiple testing correction, none of the variants were found to be
Discussion
Our results do not support pleiotropy between ET and PD, based on the top 22 SNPs identified in the ET GWAS (Muller et al., 2016) and 4 other SNPs from previous studies. As the recent GWAS identified loci associated with ET, if a significant overlap between ET and PD exists, there should be some variants that are common to both diseases. As patients who where initially diagnosed as ET have a risk to be later diagnosed as having PD (Lees et al., 2009), variants observed in both diseases may be
Disclosure statement
All authors report no conflict of interests.
Acknowledgements
The authors thank the patients and controls for their participation in the study. This work was financially supported by the Michael J. Fox Foundation. GAR holds a Canada Research Chair in Genetics of the nervous system and the Wilder Penfield Chair in Neurosciences. We thank Daniel Rochefort, Pascale Hince, Helene Catoire, Cynthia Bourassa, Pierre Provencher, Cathy Mirarchi, and Vessela Zaharieva for their assistance. We thank the Quebec Parkinson's Network and its members (http://rpq-qpn.ca/)
References (4)
- et al.
Parkinson's disease
Lancet
(2009) - et al.
The overlap between essential tremor and Parkinson disease
Parkinsonism Relat. Disord.
(2017)
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