Genetic Relationships between Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and Intelligence.

IF 2.3 4区心理学 Q3 NEUROSCIENCES

Neuropsychobiology Pub Date : 2022-01-01 DOI:10.1159/000525411

Shuquan Rao, Ancha Baranova, Yao Yao, Jun Wang, Fuquan Zhang

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引用次数: 22

Abstract

Introduction: 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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注意缺陷/多动障碍、自闭症谱系障碍和智力之间的遗传关系。

简介:注意缺陷/多动障碍(ADHD)和自闭症谱系障碍(ASD)通常同时发生;这两种特征都会对智力得分产生影响。这三种性状之间的遗传关系尚不清楚。方法:采用ADHD(20,183例，35,191例对照)、ASD(18,381例，27,969例对照)和智力(269,867名参与者)全基因组关联研究的总结结果进行分析。采用局部遗传相关分析和多基因重叠分析探讨ADHD、ASD和智力之间的共同遗传成分。使用孟德尔随机化(MR)分析来检查ADHD、ASD和智力之间的因果关系。进行了一项跨性状荟萃分析，以确定三个性状之间的多效性遗传变异。结果:我们的研究结果表明，智力与ASD和ADHD分别具有正相关和负相关的遗传关系，其中三个中心基因组区域在这三种性状之间表现出相关的遗传效应。多基因重叠分析表明，导致ADHD的所有风险变异都与一半的智力风险变异重叠，并且大多数共享变异之间的影响方向相反。大多数ASD的风险变异(80%)与几乎所有的智力风险变异(97%)重叠。值得注意的是，一些ASD/智力重叠变异对这两种情况表现出相反的影响。MR分析显示，高智商的遗传倾向与ASD风险增加(OR = 1.12)和ADHD风险降低(OR = 0.78)相关。跨性状荟萃分析鉴定出3个性状中170个多效性基因组位点，其中包括12个新位点。对新基因的功能分析支持它们可能参与神经发育。结论:我们的研究结果表明ADHD与遗传一组低智力等位基因减少有关，而ASD则是由高智力和低智力贡献等位基因混合的不协调影响导致的，这些等位基因加上额外的、与智力无关的ASD特异性风险变异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropsychobiology 医学-精神病学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.