Evaluating the Comparative Effectiveness of Genomic Health Risk Assessments for C

描述(由申请人提供)：目的：拟议的研究旨在评估基因组健康风险评估对常见慢性健康状况的比较有效性。基因组风险评分(GRS)将针对三种不同类型的健康状况：人群中正常分布的身体特征的极端(肥胖症)、医学诊断(哮喘)和精神诊断(酒精依赖)。然后，GRS将与已建立的风险评估进行比较，后者指数个人亲属健康状况的患病率，即家族史评分。分析将测试基因组信息在识别高危个人方面是否与家族史信息同等有效，以及将这两个来源的信息结合起来是否会改善风险评估。 方法：GRS将用于肥胖、哮喘和酒精依赖，从称为单核苷酸多态/ISM(SNPs)的一组风险变量中开发，这些变量已在称为全基因组关联研究(GWAS)的大规模病例对照研究中确定。GRS将使用达尼丁纵向研究的数据进行验证，该研究是一项对1037名年龄在38岁之间的人进行跟踪调查的出生队列研究，以及从美国国立卫生研究院获得的三个大型GWAS数据集。经过验证的GRS将与使用达尼丁研究数据进行的基于家族病史的风险评估进行比较。分析将考虑三种结果：(1)儿童早期发病，(2)从年轻成年到中年的慢性持续，以及(3)成年后的严重程度。对于每个结果，拟议的研究将比较 基于GRS的风险评估对使用家族史评分进行风险评估的敏感度和特异度(临床有效性)，并测试来自GRS的信息和家族史评分相结合是否提高了对高危个体的识别(临床实用性)。进一步的分析将检查临床有效性和实用性是否根据家族史和早期生命风险暴露所定义的基线风险水平而变化。 贡献和意义：这项拟议的研究将通过测试肥胖、哮喘和酒精风险评估的新方法，将基因组科学转化为公共卫生实践。 并将为评估和管理直接面向消费者的基因组检测服务提供可靠的证据基础。 公共卫生相关性：拟议的研究在两个方面与公共卫生相关：首先，它将测试一种新的健康风险评估方法，该方法可用于在症状出现之前识别高危个人。其次，它将为制定政策提供信息，以规范在健康风险评估中直接面向消费者和基于临床的基因组信息使用。对在健康风险评估中使用基因组信息的相对有效性进行测试，将有助于将基因组科学转化为公共卫生实践，并有助于制定规范使用基因组信息的政策。

DESCRIPTION (provided by applicant): Objective: The proposed research seeks to evaluate the comparative effectiveness of genomic health risk assessments for common chronic health conditions. Genomic risk scores (GRS) will be developed for three different types of health conditions: the extreme of a physical trait that is normally distributed in the population (obesity), a medical diagnosis (asthma), and a psychiatric diagnosis (alcohol dependence). GRS will then be compared to an established risk assessment which indexes the prevalence of the health condition among an individual's relatives, a family history score. Analyses will test whether genomic information is comparably effective to family history information in identifying at risk individuals and whether combining the two sources information improves risk assessment. Methods: GRS will be developed for obesity, asthma, and alcohol dependence from sets of risk variants called single nucleotide polymorph/isms (SNPs) that have been identified in massive case-control studies called genome-wide association studies (GWAS). GRS will be validated using data from the Dunedin Longitudinal Study, a birth cohort study of 1,037 individuals followed through age 38 years, and from three large GWAS datasets obtained from the National Institutes of Health. Validated GRS will be compared to family history-based risk assessments using data from the Dunedin Study. Analyses will consider three outcomes: (1) early onset in childhood, (2) chronic persistence from young adulthood through mid-life, and (3) adult severity. For each outcome, the proposed study will compare the sensitivity and specificity of GRS-based risk assessment to risk assessment using the family history score (clinical validity) and test whether combining information from the GRS and the family history score improves the identification of at risk individuals (clinical utility). Further analyses will examine whether clinical validity and utility vary depending on baseline levels of risk defined by family history and early life risk exposures. Contributions and Significance: The proposed research will inform the translation of genome science into public health practice by testing a new method of risk assessment for obesity, asthma, and alcohol dependence, and will provide a sound evidence base for the evaluation and regulation of direct-to consumer genomic testing services. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health in two ways: First, it will test a new method of health risk assessment that can be used to identify at risk individuals before symptoms develop. Second, it will inform the development of policies to regulate direct-to-consumer and clinic-based uses of genomic information in health risk assessment. Tests of the comparative effectiveness of using genomic information in health risk assessments will aid in the translation of genome science to public health practice and the development of policy to regulate the use of genomic information.