Genetic Analysis of Attention Deficit Hyperactivity Disorder

注意力缺陷多动障碍的遗传分析

• 批准号: 8149422
• 负责人: Maximilian Muenke
• 金额: $ 131.34万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149422
• 关键词: Attention deficit hyperactivity disorder; genetic analysis

Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced brain disorder with a prevalence of 3-5% in school-age children. Affected sibling pairs and densely affected multi-generation families have been recruited from Colombia, South America, the US, and Germany. A genome-wide search for loci linked to ADHD has been completed and we have identified at least five regions in the human genome that contain genes to may contribute to ADHD (Arcos-Burgos et al. 2004). To date, we have complete clinical information on a total of over 600 small and large, multi-generation families, respectively (Palacio et al., 2004; Jain et al. 2006). We are now in the process to use the clinical and genome data to search for genes that contribute to ADHD. Recently, we have identified a gene that has the highest genetic contribution to ADHD to date. In the world-wide samples statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology and treatment of ADHD (Arcos-Burgos et al. 2010).

注意缺陷多动症（ADHD）是一种受遗传影响的脑疾病，学龄儿童患病率为3-5％。从哥伦比亚，南美，美国和德国招募了受影响的兄弟姐妹对和受影响的多代家庭。 对与多动症相关的基因组的全基因组搜索已经完成，我们已经确定了人类基因组中至少有含有基因的五个区域可能会导致多动症（Arcos-Burgos等，2004）。迄今为止，我们拥有有关总共600多个小型和大型多代家族的完整临床信息（Palacio等，2004； Jain等，2006）。 现在，我们正在使用临床和基因组数据来搜索有助于多动症的基因。 最近，我们确定了迄今为止对ADHD遗传贡献最高的基因。 在全球范围内的样品中，LPHN3和ADHD的统计关联得到了证实。 功能研究表明，LPHN3变体在与注意力和活动有关的关键大脑区域中表达，影响与ADHD有关的神经回路中的代谢，并且与刺激药物的反应有关。多动症与新型非候选基因（LPHN3）的联系和复制的关联提供了有关ADHD的遗传学，神经生物学和治疗的新见解（Arcos-Burgos等人，2010年）。