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aHaihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
bSchool of Systems Biology, George Mason University, Manassas, VA, USA
cResearch Centre for Medical Genetics, Moscow, Russian Federation
dDepartment of Psychiatry, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China
eInstitute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
fDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
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Article / Publication DetailsFirst-Page Preview
Received: February 18, 2022
Accepted: May 12, 2022
Published online: June 28, 2022
Number of Print Pages: 13
Number of Figures: 4
Number of Tables: 2
ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)
For additional information: https://www.karger.com/NPS
AbstractIntroduction: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) commonly co-occur; both traits exert an influence on intelligence scores. Genetic relationships between these three traits are far from being clear. Methods: The summary results of genome-wide association studies of ADHD (20,183 cases and 35,191 controls), ASD (18,381 cases and 27,969 controls), and intelligence (269,867 participants) were used for the analyses. Local genetic correlation analysis and polygenic overlap analysis were used to explore the shared genetic components between ADHD, ASD, and intelligence. Mendelian randomization (MR) analysis was used to examine the causal associations between ADHD, ASD, and intelligence. A cross-trait meta-analysis was performed to identify pleiotropic genetic variants across the three traits. Results: Our results showed that intelligence has a positive and negative genetic correlation with ASD and ADHD, respectively, including three hub genomic regions showing correlated genetic effects across the three traits. Polygenic overlap analysis indicated that all the risk variants contributing to ADHD are overlapped with half of those for intelligence, and the majority of the shared variants have opposite effect directions between them. The majority of risk variants (80%) of ASD are overlapped with almost all the risk variants of intelligence (97%). Notably, some ASD/intelligence overlapping variants displayed opposing effects on these two conditions. MR analysis showed that the genetic liability to higher intelligence was associated with an increased risk for ASD (OR = 1.12) and a decreased risk for ADHD (OR = 0.78). Cross-trait meta-analyses identified 170 pleiotropic genomic loci across the three traits, including 12 novel loci. Functional analyses of the novel genes support their potential involvement in neurodevelopment. Conclusion: Our results suggest that ADHD is associated with inheriting a reduced set of low-intelligence alleles, whereas ASD results from incongruous effects from a mixture of high-intelligence and low-intelligence contributing alleles summed up with additional, ASD-specific risk variants not associated with intelligence.
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Received: February 18, 2022
Accepted: May 12, 2022
Published online: June 28, 2022
Number of Print Pages: 13
Number of Figures: 4
Number of Tables: 2
ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)
For additional information: https://www.karger.com/NPS
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