Web-based Phenotyping for Genome Wide Association Studies of Drug Response

基于网络的表型分析用于药物反应的全基因组关联研究

• 批准号: 7926847
• 负责人: Joanna L. MOUNTAIN
• 金额: $ 18.98万
• 依托单位: 23ANDME, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-06 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7926847
• 关键词: Adverse effects; Analgesics; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulants; Antihistamines; CYP2C19 gene; CYP2C9 gene; Code; Collection; Comprehension; Consent; Custom; Data; Gastroesophageal reflux disease; Genes; Genetic; Genetic Variation; Genotype; Goals; Grant; Individual; Institution; Insurance Carriers; Interview; Lead; Marketing; Medical; Medicine; Mind; Minor; Modeling; Nature; Online Systems; Outcome; Outcome Study; Participant; Patient Care; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Phenotype; Physicians; Play; Proton Pump Inhibitors; Publishing; Pump; Questionnaires; Research; Research Subjects; Resources; Role; Single Nucleotide Polymorphism; Staging; Structure; Surveys; Testing; Toxic effect; Variant; Warfarin; base; cohort; cost; design; dosage; drug metabolism; genetic association; genetic variant; genome wide association study; genome-wide; improved; inhibitor/antagonist; innovation; member; non-genetic; novel; public health relevance; response; success

DESCRIPTION (provided by applicant): Greater availability of personalized genetic information regarding the efficacy or toxicity of medications could lead to improved patient care and save consumers, insurers and medical institutions billions of dollars per year. Although the field of pharmacogenomics has had some success in discovering relationships between genetic variants and drug response, a great deal of genetic variation in drug response remains unexplained. Our broad, long term research aim is to identify novel pharmacogenetic associations using web-based phenotyping of efficacy and toxicity for several major drug classes. With that goal in mind, our short term aim is to determine whether web-based collection of phenotype data along with genome-wide data for thousands of 23andMe customers leads to replication of known associations between responses to proton pump inhibitors (PPIs) and the gene CYP2C19, and between responses to several commonly used medications and the gene CYP2C9. The specific aims of this study are (1) to develop and administer web-based surveys to collect information regarding response to several commonly used classes of medications (including antihistamines, analgesics, blood thinners, and proton-pump inhibitors) from at least 3,000 individuals; and (2) to determine whether this web-based research model yields replications of known associations between several commonly used medications and the genes CYP2C19 and CYP2C9. To conduct this innovative study the 23andMe research group will leverage several resources, including a broad set of drug metabolism-related single nucleotide polymorphisms (SNPs) on the 23andMe custom genotyping array. This project will also leverage involvement of a rapidly expanding, engaged, genotyped cohort of 23andMe customers who have the option to participate in research by responding to web-based questionnaires. The parallel and continuous nature of this research model allows for the efficient recruitment of participants to many studies at once and reduces the cost of re-contacting for additional analyses. As evidence of our rapid capability to assemble a cohort, an initial survey regarding commonly used medications solicited, within a month, responses from about 2500 individuals genotyped at 580,000 SNPs. Possible outcomes of this study include the replication of known pharmacogenomic associations and the discovery of novel associations. If the study is successful in yielding replications, it will set the stage for rapid, well-powered and cost-effective research on variation in response to a large number of medications, thereby significantly advancing personalized medicine. PUBLIC HEALTH RELEVANCE: The availability of personalized genetic information regarding the efficacy or toxicity of medications could lead to improved patient care, and save consumers, insurers and medical institutions billions of dollars per year. With that goal in mind, our near term aim in this grant is to determine whether web-based collection of phenotype data along with genome-wide data for thousands of 23andMe customers leads to replication of known associations two genes (CYP2C9 and CY2C19) and several major drug classes of commonly used medications.

更多关于药物疗效或毒性的个性化遗传信息的可用性可能会改善患者护理，并为消费者，保险公司和医疗机构每年节省数十亿美元。尽管药物基因组学领域在发现遗传变异和药物反应之间的关系方面取得了一些成功，但药物反应中的大量遗传变异仍然无法解释。我们广泛的，长期的研究目标是确定新的药物遗传学协会使用基于网络的表型的疗效和毒性的几个主要药物类别。考虑到这一目标，我们的短期目标是确定基于网络收集的表型数据沿着以及数千名23andMe客户的全基因组数据是否会导致对质子泵抑制剂（PPI）的反应与基因CYP 2C 19之间以及对几种常用药物的反应与基因CYP 2C 9之间的已知关联的复制。 本研究的具体目的是（1）开发和管理基于网络的调查，以收集有关几种常用药物的反应信息（包括抗组胺药、镇痛药、血液稀释剂和质子泵抑制剂）;及（2）决定该网是否─基于的研究模型产生了几种常用药物与CYP 2C 19和CYP 2C 9基因之间已知关联的复制。 为了进行这项创新研究，23andMe研究小组将利用多种资源，包括23andMe定制基因分型阵列上的一系列药物代谢相关单核苷酸多态性（SNP）。该项目还将利用23andMe客户的快速扩展，参与，基因型队列的参与，这些客户可以选择通过回答基于网络的问卷来参与研究。这种研究模式的平行和连续性允许有效地招募参与者一次参加许多研究，并减少了重新联系进行额外分析的成本。为了证明我们能够快速组建一个队列，一项关于常用药物的初步调查在一个月内从大约2500名个体中收集了580，000个SNP的基因型。 本研究的可能结果包括复制已知的药物基因组学关联和发现新的关联。如果这项研究成功地产生重复，它将为快速，有力和具有成本效益的研究奠定基础，以应对大量药物的变化，从而显着推进个性化医疗。 公共卫生相关性：关于药物疗效或毒性的个性化遗传信息的可用性可以改善患者护理，并每年为消费者，保险公司和医疗机构节省数十亿美元。考虑到这一目标，我们在这项资助中的近期目标是确定基于网络收集的表型数据沿着以及数千名23andMe客户的全基因组数据是否会导致两个基因（CYP 2C 9和CY 2C 19）和几种常用药物的主要药物类别的已知关联的复制。