EHR-based Genomic Discovery and Implementation

 描述（由申请人提供）：电子健康记录（EHR）链接的生物库具有独特的定位，可用于基因组发现和实施基因组医学以改善患者护理。在eMERGE I中，我们利用EHR连锁生物库、高密度基因分型数据和电子表型算法发现了29个与心血管性状相关的遗传位点。在eMERGE II中，我们通过进行基于EHR的随机临床试验，披露冠心病的基因组风险，并将药物基因组学信息与临床决策支持联系起来，开始实施基因组医学。eMERGE III;我们建议在我们先前工作的基础上开展一个基因组医学实施项目，以建立机制，从100个疾病相关基因的靶向测序中返回可采取行动的发现。关注两种常见的遗传疾病-家族性高胆固醇血症（FH）和家族性结直肠癌（CRC）-我们将开始将基因组发现和实施工作转化为eMERGE，以影响公共卫生。我们将从罗切斯特MN和菲尼克斯AZ的马约诊所生物库的3000名患有中度至重度高胆固醇血症或结肠息肉的受试者中获得知情同意书。DNA将被送往CLIA认证的100个疾病基因的靶向测序。我们将使用最先进的方法对变异致病性进行分类，最终确定返回的可操作变异，检查这种返回的近期结果，经济影响以及行为和心理社会后果。我们还将利用约25，000个个体的全网络数据集（具有序列数据）和现有的约50，000个个体的全网络数据集（具有与EHR相关的高密度基因型数据）进行基因组发现。我们将利用EHR的独特潜力，使用新的方法来评估多效性。与Mountain Park Health Center合作，该中心是一家为凤凰城少数墨西哥裔美国人提供服务的初级保健实践，我们将为1000名西班牙裔美国人提供高密度基因分型和表型数据，用于基因组发现和在该网站实施基因组医学的试点机制。

 DESCRIPTION (provided by applicant): Electronic health record (EHR)-linked biobanks are uniquely positioned for genomic discovery and for implementing genomic medicine to improve patient care. In eMERGE I, we leveraged an EHR-linked biobank, high-density genotyping data, and electronic phenotyping algorithms to discover 29 genetic loci associated with cardiovascular traits. In eMERGE II we began implementing genomic medicine by conducting an EHR-based randomized clinical trial of disclosing genomic risk of coronary heart disease and incorporating pharmacogenomic information in the EHR with linkage to clinical decision support. In eMERGE III; we propose to build on our prior work to conduct a genomic medicine implementation project to establish mechanisms for return of actionable findings from targeted sequencing of 100 disease-relevant genes. Focusing on two common genetic disorders-familial hypercholesterolemia (FH) and familial colorectal cancer (CRC)-we will begin to translate genomic discovery and implementation efforts in eMERGE to impact public health. We will obtain informed consent from 3000 participants of Mayo Clinic biobanks in Rochester MN and Phoenix AZ who have moderate to severe hypercholesterolemia or colon polyps. DNA will be sent for CLIA-certified targeted sequencing of 100 disease genes. We will use state-of-the-art methods to classify variant pathogenicity, finalize actionable variants for return, examine near-term outcomes, economic implications and behavioral and psychosocial consequences of such return. We will also conduct genomic discovery leveraging a network-wide data set of ~25,000 individuals with sequence data and an existing network-wide data set of ~50,000 individuals with high-density genotype data linked to the EHR. We will exploit the unique potential of the EHR to assess pleiotropy using novel approaches. In partnership with Mountain Park Health Center, a primary care practice that serves a minority population of Mexican Americans in Phoenix AZ, we will contribute high-density genotyping and phenotype data on 1000 Hispanics for genomic discovery and pilot mechanisms for implementing genomic medicine at this site.