Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer’s disease
Year: 2022
Type: article
Study design: Observational Study
Abstract: ABSTRACT Background There are very few studies investigating possible links between Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and Alzheimer’s 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 Alzheimer’s 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 Alzheimer’s. Methods We estimated the bidirectional total causal effects of genetic liability to ADHD and ASD on Alzheimer’s disease through two-sample Mendelian randomization. We investigated their direct effects, independent of educational attainment and IQ, through Multivariable Mendelian randomization. Results There 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 Alzheimer’s 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 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 to 1.44, p=0.37; ASD: OR=1.19, 95% CI: 0.94 to 1.51, p=0.14). Conclusions In the first study to date investigating the causal associations between genetic liability to ADHD, ASD and Alzheimer’s, 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.
Source: Translational Psychiatry
Institutions: University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,590
Awards: G1182606701, Reproductive and cardio-metabolic health, Neurodevelopmental disorders: what happens when children grow up and why?, G2190462495, G2253130505, G2538597952, G2786058305, Molecular, Genetic and Lifecourse Epidemiology, G3233549029, Neurodevelopmental disorders: what happens when children grow up and why?, G4056918236, Analysing the emergence of anti-microbial resistance among different bacterial species, G5260012927, Statistical Methods for Improving Causal Analyses, G5470336846, Life course aetiology of dementia and cognitive decline: improving causal inference, G6050707053, G6285097384, Mendelian randomization to hypothesis-free causal inference, G7046104286, G7194418384, G7448564355, Mediation analysis in life course epidemiology: methodological innovation and application to studies of obesity and cardiometabolic health, G7990456425, Molecular, Genetic and Lifecourse Epidemiology, G8502142660, G996504807, G997244711
OpenAlex ID: W4298396253