Genetic Epidemiology of Otitis Media

描述（由申请人提供）：中耳炎（OM）是一个全球性的儿科卫生保健问题。在美国的医生办公室实践中，它是15岁以下儿童最常见的诊断。使用双胞胎研究方法，我们最近已经证明，中耳积液（中耳积液）的时间，中耳积液的发作次数和急性中耳炎（AOM）的发作次数具有很强的遗传成分。时间的点估计遗传力为0.73。虽然有显著的证据表明，复发性/持续性OM的易感性在很大程度上是由遗传决定的，但赋予易感性的特定基因尚不清楚。我们的总体研究策略，以确定基因的基础OM是应用一个三阶段的研究设计，这将使我们能够平衡成本效益与统计能力，以检测OM基因。将招募500对有鼓膜造口管插入史的同胞（受影响）、其父母和可用的未受影响的全同胞。将从每例受试者中采集血样进行基因分型。第一阶段将对受影响的兄弟姐妹及其父母进行10 cM基因组扫描。在此阶段，我们将使用相对宽松的显著性标准（相当于LOD约为1.0）来鉴定染色体区域，以进行进一步研究，其中包括在第一阶段的阳性区域进行高密度扫描（约1 cM）。对于这种高密度扫描，将应用严格的显著性标准。最后，我们将使用基于家庭的关联/连锁不平衡分析（TDT）的单核苷酸多态性内的位置候选基因，以确定特定的基因，影响OM的易感性。本研究提出，以确定发挥作用的基因在发展中的复发/持续OM。这可能使我们能够更好地了解OM的病理生理学，从而开发更好的预防和治疗方法。

DESCRIPTION (provided by applicant): Otitis media (OM) is a worldwide pediatric health care problem. In physician office practices in the United States, it is the most common diagnosis made in children under 15 years of age. Using the twin study approach, we have recently demonstrated that time with middle ear effusion (MEE), number of episodes of MEE and number of episodes of acute otitis media (AOM) have a strong genetic component. The point estimate of heritability of time with MEE was 0.73. While there is significant evidence that susceptibility to recurrent/persistent OM is largely genetically determined, the specific genes which confer susceptibility are unknown. Our overall research strategy to identify genes underlying OM is to apply a three-stage study design that will allow us to balance cost efficiency with statistical power to detect OM genes. Five hundred pairs of siblings with a history of tympanostomy tube insertion (affected), their parent(s) and available non-affected full siblings will be recruited. A blood sample will be obtained from each subject for genotyping. The first stage will be to perform a 10 cM genome-scan in affected pairs of siblings and their parent(s). At this stage we will use a relatively generous significance criterion equivalent to a LOD of about 1.0 to identify chromosomal regions for further studies which will consist of a high density scan (approximately 1 cM) in the positive regions from the first stage. For this high-density scan a stringent significance criterion will be applied. Finally, we will use family based association/linkage disequilibrium analysis (TDT) of single nucleotide polymorphisms within positional candidate genes to identify specific genes that influence susceptibility to OM.The present study proposes to identify the genes that play a part in the development of recurrent/persistent OM. This may enable us to better understand the pathophysiology of OM and thus develop better methods for its prevention and treatment.