The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Hum Mol Genet. 2023 Jul 20;32(15):2411-2421. doi: 10.1093/hmg/ddad074.
We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit for Science). Clinically significant or susceptibility CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of attention-deficit/hyperactivity disorder (ADHD) traits (P = 5.0 × 10-3), longer response inhibition (a cognitive deficit found in several mental health and neurodevelopmental disorders; P = 1.0 × 10-2) and increased prevalence of mental health diagnoses (P = 1.9 × 10-6, odds ratio: 3.09), specifically ADHD, autism spectrum disorder anxiety and learning problems/learning disorder (P's < 0.01). There was an increased burden of rare deletions in gene-sets related to brain function or expression in brain associated with more ADHD traits. With the current mental health crisis, our data established a baseline for delineating genetic contributors in pediatric-onset conditions.
我们评估了心理健康/神经发育特征和诊断、身体健康和认知方面的基因拷贝数变异（CNV）与 7100 名无亲缘关系的欧洲或东亚血统的儿童和青少年（Spit for Science）社区样本之间的关系。临床显著或易感 CNV 存在于 3.9%的参与者中，与注意力缺陷/多动障碍（ADHD）特征的连续评分升高相关（P=5.0×10-3），反应抑制时间延长（几种心理健康和神经发育障碍中发现的认知缺陷；P=1.0×10-2），心理健康诊断的患病率增加（P=1.9×10-6，优势比：3.09），特别是 ADHD、自闭症谱系障碍、焦虑和学习问题/学习障碍（P<0.01）。与大脑功能或大脑相关表达相关的基因集的罕见缺失负担增加，与更多的 ADHD 特征相关。鉴于当前的心理健康危机，我们的数据为确定儿科发病情况的遗传因素奠定了基础。
