Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Sci Rep. 2021 Nov 19;11(1):22628. doi: 10.1038/s41598-021-01517-7.
Attention Deficit-Hyperactivity Disorder (ADHD) is a complex psychiatric and neurodevelopmental disorder that develops during childhood and spans into adulthood. ADHD's aetiology is complex, and evidence about its cause and risk factors is limited. We leveraged genetic data from genome-wide association studies (GWAS) and performed latent causal variable analyses using a hypothesis-free approach to infer causal associations between 1387 complex traits and ADHD. We identified 37 inferred potential causal associations with ADHD risk. Our results reveal that genetic variants associated with iron deficiency anemia (ICD10), obesity, type 2 diabetes, synovitis and tenosynovitis (ICD10), polyarthritis (ICD10), neck or shoulder pain, and substance use in adults display partial genetic causality on ADHD risk in children. Genetic variants associated with ADHD have a partial genetic causality increasing the risk for chronic obstructive pulmonary disease and carpal tunnel syndrome. Protective factors for ADHD risk included genetic variants associated with the likelihood of participating in socially supportive and interactive activities. Our results show that genetic liability to multiple complex traits influences a higher risk for ADHD, highlighting the potential role of cardiometabolic phenotypes and physical pain in ADHD's aetiology. These findings have the potential to inform future clinical studies and development of interventions.
注意缺陷多动障碍（ADHD）是一种复杂的精神和神经发育障碍，在儿童期发展，并持续到成年期。ADHD 的病因复杂，关于其病因和风险因素的证据有限。我们利用全基因组关联研究（GWAS）的遗传数据，并采用无假设的潜在因果变量分析方法，推断 1387 种复杂特征与 ADHD 之间的因果关系。我们确定了与 ADHD 风险相关的 37 个推断的潜在因果关系。我们的研究结果表明，与缺铁性贫血（ICD10）、肥胖、2 型糖尿病、滑膜炎和腱鞘炎（ICD10）、多发性关节炎（ICD10）、颈部或肩部疼痛以及成年人物质使用相关的遗传变异在儿童时期与 ADHD 风险存在部分因果关系。与 ADHD 相关的遗传变异具有部分遗传因果关系，增加了慢性阻塞性肺疾病和腕管综合征的风险。ADHD 风险的保护因素包括与参与社交支持和互动活动的可能性相关的遗传变异。我们的研究结果表明，多种复杂特征的遗传易感性会增加 ADHD 的风险，这突显了心脏代谢表型和身体疼痛在 ADHD 发病机制中的潜在作用。这些发现有可能为未来的临床研究和干预措施的发展提供信息。
