Evaluation of causality between ADHD and Parkinson's disease: Mendelian randomization study

Abstract

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.

Assessment of causal effects of physical activity on neurodegenerative diseases: A Mendelian randomization study

“… 21 , 22 , 23 , 24 , 25 Meanwhile, Mendelian randomization (MR) design utilizing valid instrumental variants has been applied as a robust approach to making causal inference. 26 , 27 , 28 , 29 , 30 In our study, we implemented a two-sample MR design to investigate the role of physical activity in 3 common neurodegenerative diseases: AD, PD, and ALS.…”

Non-mental diseases associated with ADHD across the lifespan: Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?

“…Conversely, no relationship was found between neonatal thyroid hormones and ADHD development. Additionally, a recent meta-analysis suggested a low, but significant association between as well maternal hyper-as hypothyroidism and ADHD in offspring, see Table 1 (Ge et al, 2020). However, methodological limitations of included studies prevented the authors from drawing strong conclusions.…”

“…One study reported that a history of asphyxia and prematurity were associated with EEG abnormalities and seizures within the ADHD population (Kartal, Aksoy, & Deda, 2017). Pre-and perinatal complications (e.g., low birth-weight, gestational age, pre-eclampsia, maternal infections and thyroid dysfunction during pregnancy) are well-established risk factors for both epilepsy and ADHD (D'Onofrio et al, 2014;Ge et al, 2020;Larsson, Sariaslan, Langstrom, D'Onofrio, & Lichtenstein, 2014;Pettersson, Larsson, D'Onofrio, Almqvist, & Lichtenstein, 2019;Silva, Colvin, Hagemann, & Bower, 2014;Walsh et al, 2017), suggesting such complications may act as shared risk factors for ADHD and epilepsy co-occurence. Other neuronal features, including frontal lobe dysfunction and adrenergic system dysregulation have been implicated in both epilepsy and ADHD (A. E. Williams et al, 2016).…”

Mendelian randomisation studies of Attention Deficit Hyperactivity Disorder

“…Mendelian randomization studies are well‐suited in studying causal effects on outcomes that happen a long time after the exposure. A study examining causal evidence with Parkinson's disease did not find strong evidence of a causal effect of ADHD genetic liability on Parkinson's disease (Li et al., 2020 ). This study did find some evidence of a causal effect in the reverse direction, which was not accounted for by body mass index (BMI) or smoking, however the authors suggest this could be driven by unmeasured confounders (Li et al., 2020 ).…”

“…A study examining causal evidence with Parkinson's disease did not find strong evidence of a causal effect of ADHD genetic liability on Parkinson's disease (Li et al., 2020 ). This study did find some evidence of a causal effect in the reverse direction, which was not accounted for by body mass index (BMI) or smoking, however the authors suggest this could be driven by unmeasured confounders (Li et al., 2020 ). A more recent study using a smaller Parkinson's disease GWAS did not find strong evidence of a causal effect on ADHD (Kim et al., 2021 ).…”