Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children.
Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children.
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DOI：
10.1186/s12993-015-0084-6
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发表时间：
2016-01-08
期刊：
影响因子：
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通讯作者：
Ayuso C
中科院分区：
文献类型：
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作者：
Gomez-Sanchez CI;Riveiro-Alvarez R;Soto-Insuga V;Rodrigo M;Tirado-Requero P;Mahillo-Fernandez I;Abad-Santos F;Carballo JJ;Dal-Ré R;Ayuso C
注意力缺陷多动障碍（ADHD）有很强的遗传成分。该研究旨在测试34种多态性与ADHD行为学的相关性，考虑到西班牙人群中临床亚型和性别的作用。290例ADHD患者和340例6-18岁的对照者被纳入病例对照研究，按性别和ADHD亚型分层。采用多因素Logistic回归分析多个变量的联合效应。在校正多次测试后，我们发现多态性与ADHD之间存在几种显着相关性（校正后的p值≤0.05）：（1）SLC 6A 4和LPHN 3在总人群中相关;（2）SLC 6A 2、SLC 6A 3、SLC 6A 4和LPHN 3在组合亚型中相关;（3）LPHN 3在男性样本中相关。多变量Logistic回归分析表明，这些因素对总样本、合并和疏忽亚型、女性和男性样本的影响分别为8.5%、14.6%、2.6%、16.5%和8.5%。我们报告的证据表明，常见变异的遗传贡献的ADHD表型在四个基因，LPHN 3基因发挥了特别重要的作用。未来的研究应该调查遗传变异对ADHD风险的贡献，考虑它们在特定性别或亚型中的作用，因为这样做可能会产生更可预测和更可靠的模型。本文的在线版本（doi：10.1186/s12993-015-0084-6）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12993-015-0084-6) contains supplementary material, which is available to authorized users.