TempO-Vseq Screen for Genomic Risk of CAD Using Blood from a Finger Prick

使用手指采血进行 TempO-Vseq 筛查 CAD 基因组风险

• 批准号: 10080400
• 负责人: BRUCE E. SELIGMANN
• 金额: $ 40.91万
• 依托单位: BIOSPYDER TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080400
• 关键词: Adherence; Affect; Age; Age-Years; American; Atrial Fibrillation; Benchmarking; Biological Assay; Blood; Cardiac; Cardiac health; Cause of Death; Cessation of life; Classification; Clinical; Coronary; Coronary Arteriosclerosis; DNA; DNA purification; DNA sequencing; Data; Data Analyses; Databases; Diabetes Mellitus; Disease; Drops; Early treatment; Edetic Acid; European; Event; Exhibits; Fingers; Freezing; Genetic Predisposition to Disease; Genetic Risk; Genomics; Genotype; Heart failure; Incidence; Ischemic Stroke; Ligation; Literature; Malignant Neoplasms; Measures; Methods; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Paper; Patients; Performance; Persons; Phase; Physicians; Prophylactic treatment; Reproducibility; Risk; Risk Assessment; Risk Factors; Saliva; Sampling; Sampling Errors; Sensitivity and Specificity; Shipping; Ships; Specificity; Sudden Death; Swab; Technology; Testing; Therapeutic; Time; Training; Tube; Utah; Variant; Whole Blood; Woman; base; biobank; clinical risk; cost; dbSNP; disease classification; disorder risk; experience; genetic variant; genome wide association study; health economics; healthy lifestyle; high risk; innovation; instrument; men; minimally invasive; prevent; programs; prophylactic; sample collection; screening; sex; success; targeted sequencing

Summary: In this Phase I program we will demonstrate the feasibility of an assay to identify subjects who have a high genetic risk of coronary artery disease (CAD) and sequelae of angina, myocardial infarction, heart failure and sudden death using a drop of whole blood spotted on filter paper (WBsf) and assayed directly without isolation of the DNA using a high throughput TempO-Seq® DNA variant targeted sequencing assay, TempO- Vseq. The variant calls and genetic risk score (GRS) determined by the TempO-Vseq assay will be benchmarked against Infinium® genotyping calls and GRS to establish performance. CAD is responsible for 1/3 of deaths in the US and world-wide. Genetic predisposition for CAD based on a polygenic GRS has been shown to be independent of conventional risk factors, including age. Large genotyping studies have been carried out that have shown that a polygenic GRS can predict risk of incident CAD events, and that prophylactic treatment with statin or adherence to a healthy lifestyle reduces incidence in subjects who are high risk. These studies have identified the variants that can be targeted to provide a GRS. The clinical rationale for a screening test based on GRS is that it can be carried out at any age, but if carried out any time before the age of 40, before clinical risk factors are typically evident, it can identify risk and afford the opportunity for early therapeutic prophylactic use of statins and/or pursuit of a healthy lifestyle. Both reduce the incidence of CAD, and if statin were to be prescribed to high-risk GRS subjects, would prevent 1 death for every 13 treated. Having identified the variants for a CAD screen to determine GRS, the need is for the lowest cost platform that provides the performance of current genotyping arrays and provides the best health economics of sample collection, shipping, storage, and assay. Advantages of the TempO-Vseq screen are expected to be 2x or greater reduction in cost, no proprietary hardware purchase required, simpler sample acquisition from a finger-prick (or if found superior in Phase II, buccal swab, or spit), simpler shipping and storage of filter paper rather than frozen blood, fully automated processing and data analysis, lower variant calling error rate than sequencing, and a weekly throughput per sequencer of >11,000 samples. The same screen augmented with additional variants could be used to identify high risk for atrial fibrillation (a leading cause of ischemic stroke), type 2 diabetes, and other contributors to CAD.

摘要：在此I阶段计划中，我们将展示评估的可行性，以识别具有 冠状动脉疾病（CAD）和心绞痛的后遗症，心肌梗塞，心力衰竭的高遗传风险 使用滤纸上发现的一滴全血（WBSF），直接分配而没有 使用高吞吐量tempo-seq®DNA变体靶向测序测定，tempo-分离DNA vseq。由TEMPO-VSEQ测定确定的变体调用和遗传风险评分（GRS）将以基准为标准 反对Infinium®基因分型呼叫和GRS以建立性能。 CAD负责1/3的死亡 美国和全球。基于多基因GRS的CAD的遗传易感性已显示为 独立于传统风险因素，包括年龄。大型基因分型研究已经进行了 已经表明，多基因GRS可以预测出现CAD事件的风险，并且预防性治疗 他汀类药物或坚持健康的生活方式会降低风险高的受试者的发病率。这些研究有 确定可以针对提供GRS的变体。基于筛查测试的临床原理 GRS是可以在任何年龄进行，但是如果在40岁之前进行临床风险之前的任何时间进行 因素通常是证据，它可以识别风险并为早期治疗性预防性使用带来机会 他汀类药物和/或追求健康的生活方式。两者都减少了CAD的事件，如果要汀类药物 规定向高风险GRS受试者的规定，可以防止每13例接受治疗1人死亡。确定了变体 对于CAD屏幕以确定GRS，需要最低的成本平台，该平台提供了性能 当前的基因分型阵列，并提供了样本收集，运输，存储和的最佳健康经济学 测定。 TEMPO-VSEQ屏幕的优势预计将为2倍或更高的成本降低，没有专家 需要购买硬件，从手指纸上采集更简单的样品（如果在第二阶段中发现优越， 颊拭子或吐口水），更简单的滤纸运输和存储而不是冷冻血液，完全自动化 处理和数据分析，比测序较低的呼叫错误率较低，每周吞吐量 > 11,000个样本的测序器。相同的屏幕增强具有其他变体，可用于识别 心房颤动的高风险（缺血性中风的主要原因），2型糖尿病和其他CAD的贡献者。