eprintid: 10099663
rev_number: 35
eprint_status: archive
userid: 608
dir: disk0/10/09/96/63
datestamp: 2020-06-09 14:31:10
lastmod: 2021-09-30 22:46:10
status_changed: 2020-06-09 14:31:10
type: article
metadata_visibility: show
creators_name: Li, GH-Y
creators_name: Ge, GM
creators_name: Cheung, C-L
creators_name: Ip, P
creators_name: Coghill, D
creators_name: Wong, I
title: Evaluation of Causality Between ADHD and Parkinson’s Disease: Mendelian Randomization study
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G11
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
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=0.930 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.
date: 2020-08
date_type: published
publisher: Elsevier
official_url: https://doi.org/10.1016/j.euroneuro.2020.06.001
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1787709
doi: 10.1016/j.euroneuro.2020.06.001
lyricists_name: Wong, Ian
lyricists_id: ICKWO00
actors_name: Wong, Ian
actors_name: Harris, Jean
actors_id: ICKWO00
actors_id: JAHAR68
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: European Neuropsychopharmacology
volume: 37
pagerange: 49-63
issn: 0924-977X
citation:        Li, GH-Y;    Ge, GM;    Cheung, C-L;    Ip, P;    Coghill, D;    Wong, I;      (2020)    Evaluation of Causality Between ADHD and Parkinson’s Disease: Mendelian Randomization study.                   European Neuropsychopharmacology , 37    pp. 49-63.    10.1016/j.euroneuro.2020.06.001 <https://doi.org/10.1016/j.euroneuro.2020.06.001>.       Green open access   
 
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document_url: https://discovery.ucl.ac.uk/id/eprint/10099663/21/Wong_Evaluation%20of%20Causality%20Between%20ADHD%20and%20Parkinson%E2%80%99s%20Disease_AAM.pdf