Gomez-Sanchez Clara I, Riveiro-Alvarez Rosa, Soto-Insuga Victor, Rodrigo Maria, Tirado-Requero Pilar, Mahillo-Fernandez Ignacio, Abad-Santos Francisco, Carballo Juan J, Dal-Ré Rafael, Ayuso Carmen
Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain.
Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain.
Behav Brain Funct. 2016 Jan 8;12(1):2. doi: 10.1186/s12993-015-0084-6.
Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population.
A cohort of ADHD 290 patients and 340 controls aged 6-18 years were included in a case-control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants.
After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively.
We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models.
注意力缺陷多动障碍（ADHD）具有很强的遗传成分。本研究旨在探讨34种多态性与ADHD症状之间的关联，并考虑临床亚型和性别的作用，研究对象为西班牙人群。
一项病例对照研究纳入了290例6至18岁的ADHD患者和340例对照，按性别和ADHD亚型分层。采用多变量逻辑回归检测多个变异的联合效应。
在进行多重检验校正后，我们发现多态性与ADHD之间存在若干显著关联（校正p值≤0.05）：（1）SLC6A4和LPHN3在总体人群中有关联；（2）SLC6A2、SLC6A3、SLC6A4和LPHN3在合并亚型中有关联；（3）LPHN3在男性样本中有关联。采用多变量逻辑回归估计这些变量对总样本、合并及注意力不集中亚型、女性和男性样本的影响，结果显示这些因素分别导致了8.5%、14.6%、2.6%、16.5%和8.5%的变异。
我们报告了四个基因中常见变异对ADHD表型的遗传贡献证据，其中LPHN3基因发挥了特别重要的作用。未来的研究应考虑遗传变异在特定性别或亚型中的作用，探讨其对ADHD风险的贡献，因为这样做可能会产生更具可预测性和稳健性的模型。
