Determining the Genetic Basis of Rotator Cuff Disease

描述（由申请人提供）： 肩袖疾病在美国很流行，有超过1700万人受到影响，每年有超过380万人就诊。尽管如此，关于其病因的信息非常有限。我们利用犹他州人口数据库（CQB）确定了发生肩袖疾病的风险增加，这强烈表明遗传易感性。除此之外，关于可能的遗传作用的数据有限。确定肩袖疾病的遗传特征可能对疾病预防和治疗产生深远的影响。本研究的目的是创建诊断为全层肩袖撕裂的患者的强大资源，包括DNA样本和完整的表型数据，并对这些患者进行全基因组关联分析，以识别与这种疾病相关的基因和/或遗传变异。 具体目标1：在3年期间从主要研究者（犹他州大学和犹他湖城盐湖VA医院执业的肩关节整形外科医生）治疗肩袖撕裂的患者人群中招募500例研究受试者。受试者将包括任何经MRI证实的肩袖全层撕裂患者。所有招募的受试者将接受病史评价、体格检查、人口统计学和家族史记录、结局问卷评价和用于遗传分析的血样采集。 具体目标二：对所有受试者进行基因分型，并利用CSTR B确定病例之间的所有遗传关系，以便在遗传分析中进行适当校正，并比较肩袖疾病家族性病例与非家族性病例的临床特征。将整合任何肩袖疾病患者的所有已知遗传关系，以确保在关联分析中避免任何偏倚。任何至少有一个一级或二级亲属也受影响的病例将被确定为“家族性”病例，并将比较家族性和非家族性组之间的临床特征（例如性别分布、年龄分布、损伤严重程度、临床结局）。 具体目标3：进行全基因组病例对照关联分析，以确定相关易感基因和变异的染色体位置。将使用Illumina 610 Q SNP标记集或等效高密度标记集对所有病例进行基因分型。将从Illumina iControl公开可用数据集中选择适当的基因组匹配对照。将对目标2中确定的遗传关系进行校正。

DESCRIPTION (provided by applicant): Rotator cuff disease is prevalent in the United States, with over 17 million individuals affected and accounting for over 3.8 million annual physician visits. Despite this, very limited information exists regarding its etiology. We have identified an increased risk for the development of rotator cuff disease utilizing the Utah Population Database (UPDB) which strongly suggests a genetic predisposition. Otherwise, there is limited data regarding a possible genetic role. Determining the genetic profile of rotator cuff disease could have profound effects on disease prevention and treatment. The purpose of this study is to create a powerful resource of patients diagnosed with full- thickness rotator cuff tears with DNA samples and complete phenotype data and to perform a genome-wide association analysis of these patients in order to identify genes and/or genetic variants associated with this disorder. Specific Aim 1: Recruit 500 study subjects over a 3-year period from a population of patients treated for rotator cuff tears by the principal investigator, an orthopaedic shoulder surgeon practicing at the University of Utah and the VA Hospital in Salt Lake City, UT. Subjects will include any patient with a MRI-confirmed full-thickness rotator cuff tear. All recruited subjects will undergo evaluation with a history, physical examination, documentation of demographic and family history, outcome questionnaire evaluation and blood sampling for genetic analysis. Specific Aim 2: Genotype all subjects and identify all genetic relationships between cases utilizing the UPDB to allow for appropriate correction in genetic analysis, and to allow comparison of clinical characteristics of familial cases of rotator cuff disease versus non-familial cases. All known genetic relationships of any of the rotator cuff disease patients will be integrated in order to ensure against any bias in the association analysis. Any case with at least one first or second degree relative also affected will be identified as a "familial" case and clinical characteristics (e.g. sex distribution, age distribution, injury severity, clinical outcomes) between familial and non-familial groups will be compared. Specific Aim 3: Perform a genome-wide case-control association analysis to determine chromosomal locations of associated predisposition genes and variants. All cases will be genotyped using the Illumina 610Q SNP marker set or equivalent high density marker set. Appropriate genomic-matched controls will be selected from the Illumina iControl publicly available data set. Correction for genetic relationships identified in Aim 2 will be made.