Background: Deciphering the genetic relationships between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) may uncover underlining shared pathophysiology as well as inform treatment.
Methods: The summary results of genome-wide association studies on ADHD, ASD, and extraversion were utilized for the analyzes. Genetic correlations between ADHD, ASD, and extraversion were tested using linkage disequilibrium score regression. Causal relationships between ADHD, ASD, and extraversion were investigated using Mendelian randomization (MR) analysis. Novel pleiotropic genomic loci shared by ADHD and ASD were identified using a cross-trait meta-analysis.
Results: Extraversion was positively correlated with ADHD (r = 0.205) and negatively correlated with ASD (r = -0.193). The MR analysis showed that ADHD confers a causal effect on ASD (OR: 1.35, 95% confidence interval (CI):1.20-1.52) and vice versa (1.46, 1.38-1.55). Extraversion exerts a causal effect on ADHD only (1.19, 1.05-1.33). The cross-trait meta-analysis identified three novel pleiotropic genomic loci for ADHD and ASD, involving two pleiotropic genes, LINC00461 and KIZ.
Conclusions: Our study provides new insights into the shared genetics of ADHD and ASD and their connections with extraversion.
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