ADHD candidate gene study in a population-based birth cohort: association with DBH and DRD2.
ADHD candidate gene study in a population-based birth cohort: association with DBH and DRD2.
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DOI：
10.1097/chi.0b013e3181579682
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发表时间：
2007-12
影响因子：
13.3
通讯作者：
Emma S. Nyman;M. N. Ogdie;A. Loukola;T. Varilo;A. Taanila;T. Hurtig;I. Moilanen;S. Loo;J. McGough;M. Järvelin;S. Smalley;S. Nelson;L. Peltonen
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文献类型：
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作者：
Emma S. Nyman;M. N. Ogdie;A. Loukola;T. Varilo;A. Taanila;T. Hurtig;I. Moilanen;S. Loo;J. McGough;M. Järvelin;S. Smalley;S. Nelson;L. Peltonen
目的注意缺陷/多动障碍（ADHD）是一种常见的儿童期发病障碍，对公众健康有重大影响。虽然基因对风险的贡献是显而易见的，但尽管进行了广泛的研究，易感的遗传决定因素在很大程度上仍然未知。到目前为止，最有希望的候选基因是那些与多巴胺和血清素通路有关的基因。本研究测试了这些候选基因中的一系列等位基因变异，以确定它们对ADHD易感性的潜在影响。方法：我们从芬兰的一个亚群的出生队列中确定了一个群体样本，其特征是奠基者效应和隔离，从而最大限度地减少了遗传异质性。研究对象采用DSM-IV ADHD诊断标准，从1986年芬兰北部出生队列的9000多名个体中系统确定，得到188例ADHD病例和166例对照。我们对13个候选基因进行了基因分型，包括多巴胺和血清素通路的关键成分。结果：我们报告了ADHD与多巴胺β -羟化酶（DBH）和多巴胺受体D2 （DRD2）基因等位变异相关的证据。结论：本研究支持多巴胺通路参与ADHD的病因学；特别是DBH和DRD2基因值得进一步研究。
OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility. METHOD We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways. RESULTS We report evidence for association of ADHD with allelic variants of the dopamine beta-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes. CONCLUSIONS Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.