Trio Analysis of Recurrent Pregnancy Loss Integrated Bioinformatics Genomics Study (TRIOS)

复发性流产综合生物信息学基因组学研究 (TRIOS) 的三重奏分析

• 批准号: 10772396
• 负责人: Ruth B Lathi
• 金额: $ 21.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10772396
• 关键词: Address; Advertisements; Affect; Anatomy; Biochemical; Bioinformatics; Biomedical Research; California; Catchment Area; Chromosome abnormality; Chromosomes; Classification; Clinical; Collection; Communities; Community Healthcare; Community Outreach; Community Physician; Complex; Counseling; Couples; DNA; Data; Databases; Diagnostic; Discipline; Disease; Disparity; Dissemination and Implementation; Education; Eligibility Determination; Enrollment; Ensure; Equity; Ethnic Origin; Etiology; Evaluation; Family; Focus Groups; Frustration; Funding; Future; Genetic; Genetic Diseases; Genetic Medicine; Genetic Predisposition to Disease; Genetic Research; Genetic Variation; Genetic study; Genomics; Geography; Goals; Health; Health Personnel; Healthcare Systems; Hematology; Heritability; Hispanic; Home; Human; Human Biology; Human Genetics; Individual; Inequity; Language; Latinx; Latinx population; Machine Learning; Medicine; Methodology; Methods; Parents; Participant; Patient Care; Patients; Perinatal; Persons; Phase; Population; Population Heterogeneity; Positioning Attribute; Precision Health; Pregnancy Outcome; Pregnancy loss; Prenatal care; Provider; Race; Recommendation; Recurrence; Reduce health disparities; Reproductive Medicine; Research; Risk; Seminal; Site; Spontaneous abortion; Test Result; Testing; Transportation; Underrepresented Populations; Variant; Work; adverse pregnancy outcome; bilingualism; cohort; community engaged research; community engagement; cost; demographics; disparity reduction; diversity and inclusion; early pregnancy; eligible participant; epidemiology study; ethnic diversity; experience; family support; gaps in access; genetic testing; genetic variant; genome sequencing; health disparity; health inequalities; human disease; improved; innovation; insight; learning strategy; machine learning method; minority engagement; multiple omics; novel; novel therapeutics; online resource; outreach; parent grant; patient population; personalized care; racial diversity; recruit; reproductive; research study; risk mitigation; sample collection; socioeconomics; therapeutic development; variant of unknown significance

PROJECT SUMMARY Recurrent pregnancy loss (RPL) affects up to 5% of families, yet nearly half of cases remain unexplained after evaluation by current testing recommendations. Unexplained euploid RPL is particularly frustrating for families and providers because there is no clear explanation nor proven therapy to mitigate risk of recurrence. As clinical presentations, subsequent pregnancy outcomes, and underlying etiologies vary widely, this complex disorder requires a precision health approach. TRIOS, the parent grant, investigates genetic causes of unexplained recurrent pregnancy loss. Genome sequencing holds immense promise for discovery of genetic variants that are lethal in humans; however, despite genetic diversity among humankind, it is well-documented that genetic studies of human disease have historically failed to capture this variation. Repeated underrepresentation of individuals of non-European ancestry has not only severely limited the understanding of genetic disease in humans, but has also led to significant ancestry-based health inequities. Conversely, increased diversity in genomic research has been shown to simultaneously increase genetic discovery and reduce health disparities. For this reason, concerted efforts to increase racial and ethnic diversity in genetic research is necessary for discovery and characterization of all disease-causing genetic variants, as well as providing equitable and personalized care to all. This supplemental proposal aims to explore and implement novel community outreach, recruitment, and enrollment methods to reduce barriers and increase minority engagement in the genetic research described in our parent grant. We will engage community physicians and front-line community healthcare workers through unstructured focus groups to better understand the threats and opportunities in enrolling their patients in research studies. Financial and transportation barriers will be minimized by facilitating enrollment and collection of samples by mail. Additionally, we will ensure research materials are accessible in Spanish, and bilingual staff are available to support families throughout all study phases. When found, we will provide actionable genetic test results to enrollees, providing personalized and direct benefit from participation in our research. Importantly, this proposed supplement will provide valuable insights into best practices for expanding geographic, socio-economic, and ancestral diversity in reproductive and genetic research. We are uniquely positioned to achieve the aims of this study due to the diverse population of Northern California, our affiliation with a far-reaching healthcare system, and a research team experienced in community-engaged research efforts. The proposed supplement is anticipated to enhance and enrich our recruitment of diverse populations for our parent grant examining genetic causes of RPL through genome sequencing, multi-omics analysis, and applied machine learning methodologies. This work will ultimately advance our understanding of RPL, inform human biology, decrease disparities, and allow for tailored diagnostics, recurrence risks, and novel therapeutics for this devastating and complex disorder.

项目摘要 复发性流产（RPL）影响多达5%的家庭，但近一半的病例在治疗后仍然无法解释。 根据当前的测试建议进行评估。不明原因的整倍体RPL对家庭来说特别令人沮丧 和供应商，因为没有明确的解释，也没有经过验证的治疗，以减轻复发的风险。作为 临床表现，随后的妊娠结局和潜在病因差异很大，这一复杂的 需要采取精确的健康方法。TRIOS，父母补助金，调查遗传原因， 不明原因的反复流产基因组测序为发现遗传物质提供了巨大的希望。 在人类中是致命的变异;然而，尽管人类的遗传多样性，它是有据可查的 人类疾病的遗传学研究历来未能捕捉到这种变异。重复 非欧洲血统的个人代表性不足不仅严重限制了对 这不仅是人类遗传疾病的主要原因，而且也导致了基于祖先的严重健康不平等。相反地， 基因组研究中的增加的多样性已被证明同时增加了遗传发现， 减少健康差距。因此，应共同努力，增加遗传学中的种族和族裔多样性， 研究对于发现和表征所有致病遗传变异是必要的， 为所有人提供公平和个性化的护理。本补充建议旨在探讨和实施 新颖的社区外展、招募和入学方法，以减少障碍，增加少数族裔 参与我们的母基金中描述的遗传研究。我们将聘请社区医生， 通过非结构化的焦点小组，前线社区卫生保健工作者更好地了解威胁 以及让患者参与研究的机会。金融和交通障碍将是 通过方便登记和通过邮件收集样本来最小化。此外，我们将确保研究 材料是西班牙语，双语工作人员可在整个研究支持家庭 阶段。一旦发现，我们将提供可操作的基因测试结果，注册，提供个性化和 直接受益于参与我们的研究。重要的是，这一拟议补充将提供宝贵的 深入了解扩大生殖领域地理、社会经济和祖先多样性的最佳做法 和基因研究。我们处于独特的地位，以实现本研究的目标，由于多样化的 北方加州的人口，我们与一个影响深远的医疗保健系统的联系，以及一个研究团队 在社区参与的研究工作经验。预计拟议补编将加强和 丰富我们的招募不同的人群，为我们的父母补助金检查RPL的遗传原因，通过 基因组测序、多组学分析和应用机器学习方法。这项工作将 最终推进我们对RPL的理解，告知人类生物学，减少差异，并允许 定制的诊断，复发风险和新的治疗方法，这种毁灭性的和复杂的疾病。