An Affected SibPair Study of ADHD in Costa Rica

哥斯达黎加 ADHD 受影响同胞对研究

• 批准号: 6868436
• 负责人: Carol A Mathews
• 金额: $ 28.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868436
• 关键词: Central America; Central American; attention deficit disorder; behavioral /social science research tag; behavioral genetics; clinical research; family genetics; genetic mapping; genetic markers; genetic susceptibility; human population genetics; human subject; mental disorder diagnosis; mental health epidemiology

DESCRIPTION (provided by applicant): This is a proposal to identify the chromosomal location of genes responsible for attention deficit hyperactivity disorder (ADHD), an inherited disorder that begins in childhood and is characterized by problems with attention, concentration, and distractibility. This goal will be achieved by studies of families with multiple affected siblings (affected sib pair or ASP families) in the genetically homogeneous population of the Central Valley of Costa Rica (CVCR). ADHD families in this population have likely inherited a susceptibility to ADHD from one or a few common ancestors. ADHD genes will be mapped by searching for genome regions that ADHD patients share identical by descent (IBD), using linkage and association studies. The study sample will consist of families with two or more siblings affected with ADHD and their parents (approximately 300 families total). Diagnostic assessment will include interviews of patients, family members, and teachers, and review of medical records. Final diagnoses will be achieved through a "best estimate" consensus process conducted by experts in diagnosing ADHD. Genealogies will be obtained for all families, who will be included in the study only if the majority of their ancestors (equal to or >5/8 great-grandparents) are of CVCR origin. The samples will be genoyped for candidate genes thought to play a role in ADHD susceptibility, as well as using markers distributed throughout the genome. Power analyses show a high probability of detecting ADHD susceptibility genes in the proposed study sample, even given etiological heterogeneity. This study is innovative in that it combines the use of linkage and association studies in a genetically isolated population, as well as using cutting edge statistical approaches to increase the power and refine the precision of the sample. Once ADHD genes are localized, fine-mapping studies can begin, ultimately leading to positional cloning efforts. Preliminary studies conducted in the CVCR show the feasibility of the sampling, diagnostic, and genotyping approaches described in this application. The sampling will be facilitated by ongoing collaborations established in the CVCR.

描述（由申请人提供）：本提案旨在确定导致注意力缺陷多动障碍（ADHD）的基因的染色体位置，这是一种始于儿童期的遗传性疾病，其特征是注意力、集中力和注意力分散问题。这一目标将通过对哥斯达黎加中央山谷 (CVCR) 遗传同质人群中具有多个受影响兄弟姐妹（受影响的兄弟姐妹或 ASP 家庭）的家庭进行研究来实现。这一人群中的多动症家族很可能从一个或几个共同祖先那里继承了对多动症的易感性。将使用连锁和关联研究，通过搜索 ADHD 患者具有相同血统 (IBD) 的基因组区域来绘制 ADHD 基因图谱。研究样本将包括有两个或更多兄弟姐妹患有 ADHD 的家庭及其父母（总共约 300 个家庭）。诊断评估将包括对患者、家庭成员和教师的访谈以及医疗记录的审查。最终诊断将通过诊断多动症专家进行的“最佳估计”共识过程来实现。将为所有家庭获取家谱，仅当其大多数祖先（等于或>5/8 曾祖父母）具有 CVCR 血统时，才会将其纳入研究。这些样本将被用于寻找被认为在多动症易感性中发挥作用的候选基因，以及使用分布在整个基因组中的标记。功效分析显示，即使存在病因异质性，在所提出的研究样本中检测到 ADHD 易感基因的可能性也很高。这项研究的创新之处在于它结合了在基因隔离群体中使用连锁和关联研究，以及使用尖端的统计方法来提高样本的功效和精确度。一旦 ADHD 基因被定位，精细定位研究就可以开始，最终导致定位克隆工作。 CVCR 中进行的初步研究表明了本申请中描述的采样、诊断和基因分型方法的可行性。 CVCR 中建立的持续合作将促进抽样工作。