Ancha Baranova1, Jun Wang2, Hongbao Cao3, Jiang-Huan Chen4, Jiu Chen5, Miao Chen6, Sulin Ni6, Xijia Xu6, Xiaoyan Ke7, Shiping Xie6, Jing Sun6, Fuquan Zhang8. 1. School of Systems Biology, George Mason University, Manassas 20110, USA; Research Centre for Medical Genetics, Moscow 115478, Russia. 2. Department of Psychiatry, Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, China. 3. School of Systems Biology, George Mason University, Manassas 20110, USA. 4. Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. 5. Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China. 6. Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China. 7. Child Mental Health Research Center, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China. 8. Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China; Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: zhangfq@njmu.edu.cn.
Abstract
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 (rg = 0.205) and negatively correlated with ASD (rg = -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.
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 (rg = 0.205) and negatively correlated with ASD (rg = -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.
Authors: Anbo Zhou; Xiaolong Cao; Vaidhyanathan Mahaganapathy; Marco Azaro; Christine Gwin; Sherri Wilson; Steven Buyske; Christopher W Bartlett; Judy F Flax; Linda M Brzustowicz; Jinchuan Xing Journal: Hum Genet Date: 2022-10-17 Impact factor: 5.881