Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, UFRGS, Avenida Bento Gonçalves, 9500, Porto Alegre, RS, CEP: 91501-970, Brazil.
ADHD Outpatient Program - Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Neuromolecular Med. 2019 Mar;21(1):60-67. doi: 10.1007/s12017-019-08525-x. Epub 2019 Jan 16.
Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD). The sample comprises 187 men diagnosed with early-onset ADHD, 135 boys diagnosed with ASD and 468 male blood donors. We tested the association of an ADGRL3 variant (rs6551665) with both early-onset ADHD and ASD susceptibility. We observed significant associations between ADGRL3-rs6551665 on ADHD and ASD susceptibilities; we found that G-carriers were at increased risk of ADHD and ASD, in accordance with previous studies. The overall evidence from the literature, corroborated by our results, suggests that ADGRL3 might be involved in brain development, and genetic modifications related to it might be part of a shared vulnerability factor associated with the underlying neurobiology of neurodevelopmental disorders such as ADHD and ASD.
神经发育障碍普遍存在,常合并发生,且具有显著的遗传相关性。先前的证据表明 ADGRL3 基因在多个样本中与注意力缺陷多动障碍(ADHD)易感性有关。鉴于 ADGRL3 在中枢神经系统发育中的功能及其先前与神经发育障碍的关联,我们旨在评估 ADGRL3 对早发性 ADHD(7 岁前)和自闭症谱系障碍(ASD)的影响。该样本包括 187 名被诊断为早发性 ADHD 的男性、135 名被诊断为 ASD 的男孩和 468 名男性献血者。我们测试了 ADGRL3 变体(rs6551665)与早发性 ADHD 和 ASD 易感性的关联。我们观察到 ADGRL3-rs6551665 与 ADHD 和 ASD 易感性之间存在显著关联;我们发现 G 携带者患 ADHD 和 ASD 的风险增加,这与先前的研究一致。文献中的综合证据,加上我们的结果,表明 ADGRL3 可能参与大脑发育,与其相关的遗传修饰可能是与 ADHD 和 ASD 等神经发育障碍的潜在神经生物学相关的共同脆弱性因素的一部分。