eprintid: 10182228
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/18/22/28
datestamp: 2023-11-28 14:24:53
lastmod: 2023-11-28 14:24:53
status_changed: 2023-11-28 14:24:53
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Pagoni, Panagiota
creators_name: Dardani, Christina
creators_name: Leppert, Beate
creators_name: Korologou-Linden, Roxanna
creators_name: Smith, George Davey
creators_name: Howe, Laura D
creators_name: Anderson, Emma L
creators_name: Stergiakouli, Evie
title: Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer's disease
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D79
divisions: FH5
keywords: Science & Technology, Life Sciences & Biomedicine, Psychiatry, DEFICIT-HYPERACTIVITY DISORDER, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, AGE-DEPENDENT DECLINE, MENDELIAN RANDOMIZATION, SPECTRUM DISORDERS, LATE-ONSET, FOLLOW-UP, INSTRUMENTS, CHILDHOOD, IMPACT
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abstract: Few studies suggest possible links between attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and Alzheimer’s disease but they have been limited by small sample sizes, diagnostic and recall bias. We used two-sample Mendelian randomization (MR) to estimate the bidirectional causal association between genetic liability to ADHD and ASD on Alzheimer’s disease. In addition, we estimated the causal effects independently of educational attainment and IQ, through multivariable Mendelian randomization (MVMR). We employed genetic variants associated with ADHD (20,183 cases/35,191 controls), ASD (18,381 cases/27,969 controls), Alzheimer’s disease (71,880 cases/383,378 controls), educational attainment (n = 766,345) and IQ (n = 269,867) using the largest GWAS of European ancestry. There was limited evidence to suggest a causal effect of genetic liability to ADHD (odds ratio [OR] = 1.00, 95% CI: 0.98–1.02, P = 0.39) or ASD (OR = 0.99, 95% CI: 0.97–1.01, P = 0.70) on Alzheimer’s disease. Similar causal effect estimates were identified as direct effects, independent of educational attainment (ADHD: OR = 1.00, 95% CI: 0.99–1.01, P = 0.76; ASD: OR = 0.99, 95% CI: 0.98–1.00, P = 0.28) and IQ (ADHD: OR = 1.00, 95% CI: 0.99–1.02. P = 0.29; ASD: OR = 0.99, 95% CI: 0.98–1.01, P = 0.99). Genetic liability to Alzheimer’s disease was not found to have a causal effect on risk of ADHD or ASD (ADHD: OR = 1.12, 95% CI: 0.86–1.44, P = 0.37; ASD: OR = 1.19, 95% CI: 0.94–1.51, P = 0.14). We found limited evidence to suggest a causal effect of genetic liability to ADHD or ASD on Alzheimer’s disease; and vice versa.
date: 2022-10-01
date_type: published
publisher: SPRINGERNATURE
official_url: https://doi.org/10.1038/s41398-022-02150-2
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1993273
doi: 10.1038/s41398-022-02150-2
medium: Electronic
pii: 10.1038/s41398-022-02150-2
lyricists_name: Anderson, Emma
lyricists_id: ELAND55
actors_name: Anderson, Emma
actors_id: ELAND55
actors_role: owner
funding_acknowledgements: BR16/028 [BRACE Alzheimer's charity]; [University of Bristol]; MR/M020894/1 [UK Medical Research Council]; MR/P014437/1 [UK Medical Research Council]; MC_UU_00011/1 [UK Medical Research Council]; MC_UU_00011/3 [UK Medical Research Council]; MC_UU_00011/6 [UK Medical Research Council]; 108902/B/15/Z [Wellcome Trust]; 204895/Z/16/Z [Wellcome Trust]; 215193/Z18/Z [Wellcome Trust]
full_text_status: public
publication: Translational Psychiatry
volume: 12
number: 1
article_number: 422
pages: 7
event_location: United States
citation:        Pagoni, Panagiota;    Dardani, Christina;    Leppert, Beate;    Korologou-Linden, Roxanna;    Smith, George Davey;    Howe, Laura D;    Anderson, Emma L;           Pagoni, Panagiota;  Dardani, Christina;  Leppert, Beate;  Korologou-Linden, Roxanna;  Smith, George Davey;  Howe, Laura D;  Anderson, Emma L;  Stergiakouli, Evie;   - view fewer <#>    (2022)    Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer's disease.                   Translational Psychiatry , 12  (1)    , Article 422.  10.1038/s41398-022-02150-2 <https://doi.org/10.1038/s41398-022-02150-2>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10182228/1/s41398-022-02150-2.pdf