Paris Brain Institute, F-75013, Paris, France; Inserm, U 1127, F-75013, Paris, France; CNRS, UMR 7225, F-75013, Paris, France; Sorbonne Université, F-75013, Paris, France; Inria Paris, Aramis Project-team, F-75013, Paris, France.
Paris Brain Institute, F-75013, Paris, France; Inserm, U 1127, F-75013, Paris, France; CNRS, UMR 7225, F-75013, Paris, France; Sorbonne Université, F-75013, Paris, France; Inria Paris, Aramis Project-team, F-75013, Paris, France; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Parkinsonism Relat Disord. 2021 May;86:74-77. doi: 10.1016/j.parkreldis.2021.04.003. Epub 2021 Apr 11.
To study the association between impulse control disorders (ICDs) in Parkinson's disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits).
In absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD.
We searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson's Progression Markers Initiative database (N = 368, 33% female, age range = [33-84]) and the Drug Interaction With Genes in Parkinson's Disease study (N = 373, 40% female, age range = [29-85]).
We considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis.
Albeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.
研究帕金森病（PD）冲动控制障碍（ICD）与 40 种已知或假定风险因素（如抑郁、人格特质）的遗传风险评分（GRS）之间的关联。
由于缺乏已发表的全基因组关联研究（GWAS），因此对 PD 中 ICD 的遗传学知之甚少。对于具有大量 GWAS 可用的相关表型的 GRS，可能有助于阐明 PD 中 ICD 的遗传贡献者。
我们搜索了在欧洲血统人群中进行的 GWAS，这些人群的汇总统计数据可公开获得，涵盖了广泛的表型，包括其他精神障碍、人格特质和简单表型。我们分别在两个具有临床和遗传数据的最大 PD 队列中测试了它们的预测能力：帕金森病进展标志物倡议数据库（N=368，33%为女性，年龄范围=[33-84]）和药物相互作用与帕金森病中的基因研究（N=373，40%为女性，年龄范围=[29-85]）。
我们考虑了 40 种已知或假定的 PD 中 ICD 风险因素，这些因素已经发表了大型 GWAS。经过多重比较的 Bonferroni 校正后，没有 GRS 或 40 个 GRS 的组合与每个队列的分析以及荟萃分析中的 ICD 显著相关。
尽管我们的方法不成功，但随着 PD 临床队列中基因型的可用性增加，以及我们所考虑的表型的 GWAS 样本量的增加，它将在未来几年获得更多的权力。我们的方法可应用于其他复杂疾病，这些疾病目前没有或有限的 GWAS。
