An Affected SibPair Study of ADHD in Costa Rica

描述(由申请人提供)：这是一项确定注意力缺陷多动障碍(ADHD)基因染色体位置的建议，ADHD是一种遗传性疾病，始于儿童时期，特征是注意力、注意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)遗传同质性人口中有多个受影响兄弟姐妹的家庭(受影响的兄弟姐妹对或ASP家庭)进行研究来实现。这个群体中的ADHD家庭很可能从一个或几个共同的祖先那里遗传了ADHD的易感性。利用连锁和关联研究，将通过搜索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)。诊断性评估将包括对患者、家属和教师的面谈，以及对医疗记录的审查。最终的诊断将通过专家在诊断ADHD方面进行的“最佳估计”共识过程来实现。将获得所有家庭的家谱，只有当他们的大多数祖先(等于或&gt；5/8曾祖父母)是CVCR血统时，他们才会被包括在研究中。这些样本将使用分布在整个基因组中的标记，对被认为在ADHD易感性中起作用的候选基因进行基因分型。能量分析表明，即使在给定的病因学异质性的情况下，在所建议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，它结合了遗传隔离群体中的连锁和关联研究，以及使用尖端统计方法来提高样本的能力和精确度。一旦ADHD基因定位，就可以开始精细定位研究，最终导致定位克隆工作。在CVCR中进行的初步研究表明，本申请中描述的采样、诊断和基因分型方法是可行的。采样将通过在CVCR中建立的持续合作来促进。

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.