Parkinson's disease polygenic risk score is not associated with impulse control disorders: A longitudinal study

被引:12
|
作者
Ihle, J. [1 ]
Artaud, F. [2 ]
Bekadar, S. [1 ]
Mangone, G. [1 ]
Sambin, S. [1 ]
Mariani, L. L. [1 ]
Bertrand, H. [1 ]
Rascol, O. [3 ,4 ,5 ]
Durif, F. [6 ]
Derkinderen, P. [7 ]
Scherzer, C. [8 ,9 ,10 ]
Elbaz, A. [2 ]
Corvol, J. C. [1 ]
Corvol, Jean-Christophe [11 ]
Elbaz, Alexis [11 ,12 ]
Vidailhet, Marie [11 ]
Brice, Alexis [11 ]
Artaud, Fanny [13 ]
Bourdain, Frederic [13 ]
Brandel, Jean-Philippe [14 ]
Derkinderen, Pascal [15 ]
Durif, Franck [16 ]
Levy, Richard [17 ]
Pico, Fernando [18 ]
Rascol, Olivier [19 ]
Bonnet, Anne-Marie [11 ]
Bonnet, Cecilia [11 ]
Brefel-Courbon, Christine [19 ]
Cormier-Dequaire, Florence [11 ]
Degos, Bertrand [11 ]
Debilly, Berangere [16 ]
Galitsky, Monique [19 ]
Grabli, David [11 ]
Hartmann, Andreas [11 ]
Klebe, Stephan [11 ]
Kraemmer, Julia [11 ]
Lacomblez, Lucette [11 ]
Leder, Sara [11 ]
Mangone, Graziella [11 ]
Mariani, Louise-Laure [11 ]
Marques, Ana-Raquel [16 ]
Mesnage, Valerie [17 ]
Muellner, Julia [11 ]
Ory-Magne, Fabienne [19 ]
Plante-Bordeneuve, Violaine [20 ]
Roze, Emmanuel [11 ]
Tir, Melissa [18 ]
You, Hana [11 ]
Benchetrit, Eve [11 ]
Socha, Julie [11 ]
机构
[1] Sorbonne Univ, Pitie Salpetriere Hosp, INSERM, ICM,Dept Neurol,CNRS,NS PARK FCRIN Network, Paris, France
[2] Univ Paris Sud, Univ Paris Saclay, Inst Natl Sante & Rech Med, Fac Med FA AE,Fac Med,UVSQ,CESP, Villejuif, France
[3] Univ Toulouse 3, CHU Toulouse, Toulouse, France
[4] Ctr Invest Clin CIC1436, INSERM, NS PARK FCRIN Network, Dept Neurosci,NeuroToul COEN Ctr, Toulouse, France
[5] Ctr Invest Clin CIC1436, INSERM, NS PARK FCRIN Network, NeuroToul COEN Ctr,Dept Pharmacol Clin, Toulouse, France
[6] CHU Clermont Ferrand, Dept Neurol, NS PARK FCRIN Network, Clermont Ferrand, France
[7] CHU Nantes, Dept Neurol, NS PARK FCRIN Network, Nantes, France
[8] Brigham & Womens Hosp, Ctr Adv Parkinsons Dis Res, Boston, MA 02115 USA
[9] Harvard Med Sch, Boston, MA 02115 USA
[10] Harvard Med Sch, Brigham & Womens Hosp, Precis Neurol Program, Boston, MA 02115 USA
[11] Hop La Pitie Salpetriere, Paris, France
[12] CESP, Villejuif, France
[13] CH Foch, Suresnes, France
[14] Fdn Adolphe De Rothschild, Paris, France
[15] CHU, Nantes, France
[16] CHU Clermont, Ferrand, France
[17] CHU St Antoine, Paris, France
[18] CH, Versailles, France
[19] CHU, Toulouse, France
[20] Henri Mondor Hosp, Creteil, France
[21] ICM, INSERM, Paris, France
[22] Hop St Louis, Paris, France
关键词
D O I
10.1016/j.parkreldis.2020.03.017
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To examine the relationship between a Parkinson's disease (PD) polygenic risk score (PRS) and impulse control disorders (ICDs) in PD. Background: Genome wide association studies (GWAS) have brought forth a PRS associated with increased risk of PD and younger disease onset. ICDs are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. It is unknown whether ICDs and PD share genetic susceptibility. Methods: We used data from a multicenter longitudinal cohort of PD patients with annual visits up to 6 years (DIG-PD). At each visit ICDs, defined as compulsive gambling, buying, eating, or sexual behavior were evaluated by movement disorders specialists. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted PRS based on 90 SNPs associated with PD. We estimated the association between PRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for dopaminergic treatment and other known risk factors for ICDs. Results: Of 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p < 0.001) as well as higher PRS values (p = 0.06). At baseline, there was no association between the PRS and ICDs (overall, p = 0.84). The prevalence of ICDs increased over time similarly across the quartiles of the PRS (overall, p = 0.88; DA users, p = 0.99). Conclusion: Despite younger disease onset being associated with both higher PRS and ICD prevalence, our findings are not in favor of common susceptibility genes for PD and ICDs.
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收藏
页码:30 / 33
页数:4
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