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 note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 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