Family Linkage Study of Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停的家庭关联研究

• 批准号: 7281742
• 负责人: Allan I Pack
• 金额: $ 113.02万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281742
• 关键词: Acoustic Rhinometry; Address; Affect; Age; Alleles; Blood; Candidate Disease Gene; Cardiovascular Diseases; Chromosome Mapping; Clinical Research; Commit; Communities; Complement; Complex; Continuous Positive Airway Pressure; DNA; Data; Databases; Depth; Development; Diagnosis; Disease; Etiology; Europe; Extended Family; Family; Family Study; Fatty acid glycerol esters; Frequencies; Gender; Genealogy; Genes; Genetic; Genetic Research; Genome; Genotype; Goals; Grant; Haplotypes; Hereditary Disease; Hospitals; Hypertension; Iceland; Imaging Techniques; Individual; Insulin Resistance; Investigation; Island; Lateral; Life; Link; Magnetic Resonance Imaging; Meiosis; Menopausal Status; Mutation; Names; Nature; Non obese; Nose; Numbers; Obesity; Obstructive Sleep Apnea; Patients; Pattern; Pennsylvania; Persons; Pharyngeal structure; Phenotype; Play; Population; Population Study; Prevalence Study; Published Comment; Relative (related person); Relative Risks; Research Infrastructure; Resistance; Resources; Risk; Risk Factors; Role; Scotland; Sleep; Sleep Apnea Syndromes; Soft Palate; Stroke; Structure; Subjects Selections; Susceptibility Gene; Techniques; Testing; Time; Tongue; United States; Universities; Welts; base; case control; clinically significant; computerized; craniofacial; family structure; genetic analysis; genetic linkage analysis; genetic pedigree; genome-wide linkage; programs; size; soft tissue; tool; trait; validation studies

DESCRIPTION: (provided by applicant) There is family aggregation of obstructive sleep apnea (OSA) as has been shown in the United States, Europe and recently in Iceland. Iceland represents a unique opportunity for genetic research. It is a community that was settled by founders in the 9 th Century, and has developed in relative isolation since that time to its present size of 285,000 persons. Moreover, there is a commitment to record keeping that has allowed deCODE Genetics, who are collaborators on this grant, to develop a computerized genealogy data base that permits the ancestry of individuals to be traced over centuries. This tool, together with the founder nature of the population, makes possible a unique genealogy-driven approach to study the genetics of complex disorders, an approach that has already been successful. We propose in this application to study the genetic basis of the common disorder---obstructive sleep apnea--using this genealogical approach. The study will be built on patients with the disorder, who have already been diagnosed in Iceland and where large family pedigrees have been identified. The proposed study involves a genome-wide family linkage investigation. This will be conducted with an affected only approach examining allele sharing between affected individuals using 1,100 markers spaced across the genome. We plan to oversample the relatively non-obese subjects providing us the opportunity to evaluate linkage in both relatively non-obese and obese subjects. The linkage study will be complemented with an association study, with unrelated cases and controls, matched for age, gender, and menopausal status. In the association study, we will, as a primary aim, test candidate genes arising from the linkage study and, as a secondary aim, evaluate candidate genes that we believe will be identified in the ongoing Cleveland Family Study. A subset of subjects in both the family linkage and association study, will have in-depth phenotyping to determine whether there are sub-phenotypes for this complex disorder and, if so, whether they aggregate in families. This in depth phenotyping will involve upper airway magnetic resonance imaging to evaluate upper airway soft tissue and craniofacial structures, acoustic rhinometry to quantify nasal resistance, a known risk factor for the disorder, and insulin resistance. We will explore whether there are distinct patterns of linkage for the different sub-phenotypes. To accomplish this large genetic study, we have put together the resources of three major organizations--the University of Pennsylvania, the University of Iceland Hospitals, and deCODE Genetics. We propose to leverage the truly unique infrastructure developed by deCODE Genetics, the clinical research programs in sleep apnea at the University of Iceland Hospitals, and the in-depth phenotyping expertise at the University of Pennsylvania to accomplish our goals.

描述：（由申请人提供）阻塞性睡眠呼吸暂停 (OSA) 存在家庭聚集现象，这在美国、欧洲以及最近在冰岛都有体现。冰岛为基因研究提供了独特的机会。这是一个由创始人于 9 世纪定居的社区，自那时起在相对孤立的环境中发展到目前的 285,000 人规模。 此外，由于对记录保存的承诺，使得deCODE Genetics（该资助的合作者）能够开发一个计算机化的家谱数据库，允许在几个世纪以来追踪个人的祖先。这一工具与人群的创始人性质一起，使得一种独特的谱系驱动的方法来研究复杂疾病的遗传学成为可能，这种方法已经取得了成功。我们在此申请中建议使用这种谱系方法来研究常见疾病——阻塞性睡眠呼吸暂停的遗传基础。这项研究将以患有这种疾病的患者为基础，这些患者已经在冰岛被诊断出来，并且已经确定了大家族谱系。拟议的研究涉及全基因组家族连锁调查。 这将采用仅受影响的方法进行，使用跨基因组间隔的 1,100 个标记检查受影响个体之间的等位基因共享。我们计划对相对不肥胖的受试者进行过度抽样，为我们提供评估相对不肥胖和肥胖受试者之间的联系的机会。关联研究将得到关联研究的补充，其中包括不相关的病例和对照，并匹配年龄、性别和绝经状况。在关联研究中，我们的主要目标是测试连锁研究中产生的候选基因，次要目标是评估我们认为将在正在进行的克利夫兰家庭研究中确定的候选基因。家庭联系和关联研究中的一部分受试者将进行深入的表型分析，以确定这种复杂疾病是否存在亚表型，如果有，它们是否聚集在家庭中。这种深入的表型分析将涉及上气道磁共振成像以评估上气道软组织和颅面结构，声学鼻测量以量化鼻阻力（该疾病的已知危险因素）和胰岛素抵抗。我们将探讨不同亚表型是否存在不同的连锁模式。为了完成这项大型基因研究，我们汇集了三个主要组织的资源——宾夕法尼亚大学、冰岛大学医院和 deCODE Genetics。我们建议利用 deCODE Genetics 开发的真正独特的基础设施、冰岛大学医院的睡眠呼吸暂停临床研究项目以及宾夕法尼亚大学深入的表型专业知识来实现​​我们的目标。

项目成果

Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea.

夜间鼻塞很常见，会降低阻塞性睡眠呼吸暂停患者的睡眠质量。

• 发表时间: 2018-08
• 影响因子: 4.4
• 作者: Värendh, Maria;Andersson, Morgan;Bjørnsdottir, Erla;Hrubos;Johannisson, Arne;Arnardottir, Erna S;Gislason, Thorarinn;Juliusson, Sigurdur
• 通讯作者: Juliusson, Sigurdur