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

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.