INTERMEDIATE TRAITS FOR SLEEP APNEA

睡眠呼吸暂停是一种常见的疾病，影响4%的中年男性和 2%的中年女性。最近有证据表明，有一个 本病患者一级亲属的遗传影响 障碍会增加患阻塞性睡眠呼吸暂停的风险。这个 这种增加的家族性风险的基础尚不明确。我们假定 有三个特定的中间性状，每一个都降低了 呼吸道大小，从而增加睡眠呼吸暂停的风险。这些 中间性状包括：a)大鼠在 颈部；b)头面部结构；以及c)关键软组织的大小 呼吸道(软腭部、舌部、咽侧壁)。所有这些都是 风险因素可以使用先进的磁力进行定量评估 磁共振成像(MRI)和新的体积图像分析技术 这是我们开发的。我们建议，建立 睡眠呼吸暂停的遗传学基础是识别不同的中间体 包括使用成像技术的特征。因此，我们提出一个案例-- 睡眠呼吸暂停的结构性危险因素对照研究。 这项病例对照研究将得到对儿童兄弟姐妹的研究的补充 患者和对照，以确定这些特征表明 家庭聚集不是由共同的环境因素解释的。我们 相信这些结构性风险因素将相互作用，增加 睡眠呼吸暂停的风险。上呼吸道结构风险的阐明 因素将为开发新的、更有效的产品提供基础 睡眠呼吸暂停筛查技术为临床提供依据 用于进行未来的DNA分析，目的是确定 这些风险因素。这一建议是基于这样一个假设，即具体的 中间特征会增加睡眠呼吸暂停的风险，而这些 中间性状表现为家族聚集性。我们的具体目标 包括：1)量化上呼吸道颅面结构、软组织和 三维磁共振成像在局部脂肪沉积中的应用 为了确定与梗阻相关的中间性状 在正常人和呼吸暂停患者中使用病例对照设计的睡眠呼吸暂停； 确定睡眠呼吸暂停的上呼吸道结构危险因素 表现出家族聚集性，最有可能有基因 通过比较先证者、先证者的兄弟姐妹、邻居 控件和邻居控件的同级控件。我们的资源，这是 包括广泛临床睡眠实践、复杂的磁共振成像 技术，新的体积计算机图形图像分析和 分子流行病学、头面部结构、遗传学方面的专业知识 减少肥胖将使我们能够实现我们的特定目标。

Sleep apnea is a common condition that affects 4% of middle-aged males and 2% of middle-aged females. There is recent evidence that there is a genetic influence since first degree relatives of patients with this disorder have an increased risk of having obstructive sleep apnea. The basis for this increased familial risk is undefined. We postulate that there are three specific intermediate traits, each of which reduces upper airway size, thereby increasing the risk of sleep apnea. These intermediate traits include: a) particular distribution of rat in the neck; b) craniofacial structure; and c) size of critical soft tissues in the airway (soft palate, tongue, lateral pharyngeal walls). All of these risk factors can be assessed quantitatively using advanced magnetic resonance imaging (MRI) and novel volumetric image analysis techniques that we have developed. We propose that the first step to establish the genetic basis for sleep apnea is to identify the different intermediate traits involved using the imaging technology. Hence, we propose a case- control study to identify the structural risk factors for sleep apnea. This case-control study will be complemented by studies in siblings of the patients and controls in order to identify those traits that demonstrate family aggregation not explained by shared environmental factors. We believe that these structural risk factors will interact to increase the risk of sleep apnea. The elucidation of upper airway structural risk factors will provide the basis for developing new, more effective techniques for screening patients for sleep apnea and provide the basis for performing future DNA analysis aimed at identify the genetic loci for these risk factors. This proposal is based on the hypothesis that specific intermediate traits increase the risk for sleep apnea and that these intermediate traits demonstrate family aggregation. Our specific aims are: 1) to quantify upper airway craniofacial structure, soft tissues and regional fat deposition using three dimensional magnetic resonance imaging in order to determine the intermediate traits associated with obstructive sleep apnea utilizing a case control design in normals and apneics; and 2) to determine the upper airway structural risk factors for sleep apnea that demonstrate family aggregation and are most likely to have a genetic component by comparing probands, siblings of probands, neighborhood controls and siblings of neighborhood controls. Our resources, which include an extensive clinical sleep practice, sophisticated MR imaging techniques, novel volumetric computer graphics image analysis and expertise in molecular epidemiology, craniofacial structure, the genetics of obesity will allow us to achieve our specific aims.