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bioRxiv · 10.1101/2020.04.15.043380

Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer's disease

Pagoni, P.·Dardani, C.·Leppert, B.·Korologou-Linden, R.·Davey Smith, G.·Howe, L. D.·Anderson, E. L.·Stergiakouli, E.
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Abstract

BackgroundThere are very few studies investigating possible links between Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and Alzheimers disease and these have been limited by small sample sizes, diagnostic and recall bias. However, neurocognitive deficits affecting educational attainment in individuals with ADHD could be risk factors for Alzheimers later in life while hyper plasticity of the brain in ASD and strong positive genetic correlations of ASD with IQ and educational attainment could be protective against Alzheimers. MethodsWe estimated the bidirectional total causal effects of genetic liability to ADHD and ASD on Alzheimers disease through two-sample Mendelian randomization. We investigated their direct effects, independent of educational attainment and IQ, through Multivariable Mendelian randomization. ResultsThere was limited evidence to suggest that genetic liability to ADHD (OR=1.00, 95% CI: 0.98 to 1.02, p=0.39) or ASD (OR=0.99, 95% CI: 0.97 to 1.01, p=0.70) was associated with risk of Alzheimers disease. Similar causal effect estimates were identified when the direct effects, independent of educational attainment (ADHD: OR=1.00, 95% CI: 0.99 to 1.01, p=0.07; ASD: OR=0.99, 95% CI: 0.98 to 1.00, p=0.28) and IQ (ADHD: OR=1.00, 95% CI: 0.99 to 1.02. p=0.29; ASD: OR=0.99, 95% CI: 0.98 to 1.01, p=0.99), were assessed. Finally, genetic liability to Alzheimers disease was not found to have a causal effect on risk of ADHD or ASD (ADHD: OR=1.12, 95% CI: 0.86 to 1.44, p=0.37; ASD: OR=1.19, 95% CI: 0.94 to 1.51, p=0.14). ConclusionsIn the first study to date investigating the causal associations between genetic liability to ADHD, ASD and Alzheimers, within an MR framework, we found limited evidence to suggest a causal effect. It is important to encourage future research using ADHD and ASD specific subtype data, as well as longitudinal data in order to further elucidate any associations between these conditions.

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Pagoni, P., Dardani, C., Leppert, B., Korologou-Linden, R., Davey Smith, G., Howe, L. D., Anderson, E. L., Stergiakouli, E.. 2020-04-17. Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer's disease. https://doi.org/10.1101/2020.04.15.043380

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