Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Eur Neuropsychopharmacol. 2020 Aug;37:49-63. doi: 10.1016/j.euroneuro.2020.06.001. Epub 2020 Jun 18.
In a retrospective cohort study, patients with attention-deficit hyperactivity disorder (ADHD) and psychostimulant prescription were associated with increased risk of Parkinson's disease (PD). It is unclear whether ADHD per se or psychostimulant prescription is associated with PD. We aim to determine if genetic correlation or/and causal association exists between ADHD and PD using summary statistics obtained from the largest meta-analysis of genome-wide association studies of ADHD (20,183 cases; 35,191 controls) and PD (26,421 cases; 442,271 controls). Genetic correlation was tested between ADHD and PD by linkage disequilibrium score regression. Causal estimate was assessed by inverse-variance weighted (IVW) method as the main mendelian randomization analysis, with sensitivity analyses to detect horizontal pleiotropy. Weak and inverse genetic correlation existed between ADHD and PD (r=-0.100;SE=0.045;P = 0.026). Univariable IVW analysis with 10 and 77 genetic instruments respectively revealed null association for ADHD with PD (OR=0.930 per doubling in odds of ADHD; 95% CI:0.792-1.092) and PD with ADHD (OR=0.986 per doubling in odds of PD; 95% CI:0.956-1.015). Multivariable IVW analyses adjusted for BMI/smoking also revealed null association of ADHD with PD. Using 58 PD-associated genetic instruments, multivariable IVW analysis with/without adjustment for BMI/smoking suggested a weak and inverse causal association for PD on ADHD, but cautious interpretation is required. This well-powered study did not support causality between ADHD and PD. The observed positive association between ADHD and PD is more likely to be caused by unmeasured confounders. As psychostimulant use is associated with high risk of early-onset PD, future research should focus on this area.
在一项回顾性队列研究中，患有注意力缺陷多动障碍 (ADHD) 和精神兴奋剂处方的患者患帕金森病 (PD) 的风险增加。目前尚不清楚是 ADHD 本身还是精神兴奋剂处方与 PD 相关。我们旨在使用最大的 ADHD（20,183 例；35,191 例对照）和 PD（26,421 例；442,271 例对照）全基因组关联研究的汇总统计数据，确定 ADHD 和 PD 之间是否存在遗传相关性或因果关系。通过连锁不平衡得分回归测试 ADHD 和 PD 之间的遗传相关性。通过逆方差加权（IVW）方法作为主要孟德尔随机分析评估因果估计，进行敏感性分析以检测水平偏倚。ADHD 和 PD 之间存在微弱的负遗传相关性（r=-0.100；SE=0.045；P=0.026）。使用 10 个和 77 个遗传工具分别进行的单变量 IVW 分析表明，ADHD 与 PD 之间的关联为零（ADHD 几率每增加一倍，OR=0.930；95%CI：0.792-1.092），PD 与 ADHD 之间的关联也为零（PD 几率每增加一倍，OR=0.986；95%CI：0.956-1.015）。调整 BMI/吸烟因素的多变量 IVW 分析也显示 ADHD 与 PD 之间的关联为零。使用 58 个 PD 相关的遗传工具，在调整/不调整 BMI/吸烟因素的情况下进行多变量 IVW 分析表明，PD 对 ADHD 存在微弱的负向因果关系，但需要谨慎解释。这项有力的研究不支持 ADHD 和 PD 之间的因果关系。ADHD 和 PD 之间观察到的正相关更可能是由未测量的混杂因素引起的。由于精神兴奋剂的使用与早发性 PD 的高风险相关，未来的研究应集中在这一领域。
