Genome-wide genotyping of existing samples in the California Teachers Study cohort from under-represented racial & ethnic minority groups to facilitate broad and open future research

项目总结/摘要 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 22-056.该资助机会的目标是增加样本和数据的代表性， 种族/族裔少数群体的资料。包括更多的样本， 在这些知识库中代表性不足的种族/少数民族人口是必要的，但还不够， 实现这一目标。迄今为止，大多数人类基因组研究都集中在欧洲人的同源性上。 根据遗传祖先定义的人口，并排除多种族个体。排斥多种族 个人从该研究增加了机会，其产品-包括参考面板， 多基因风险评分（PRSes）-在其他非基因组中发现和翻译的有效性较低， 欧洲和混合人口。这在美国尤其令人担忧，其中“多数”的数目- “少数民族”国家正在增加，多种族人口增加了近300%（从900万到2000万）。 自2010年人口普查以来，约有3400万人。更广泛和更深入的数据来自不同和多种族的个人 和人口对于解开种族、民族、血统、生物学和 关于健康风险、结果和差距的文化结构。我们的加州教师研究（CTS），一个癌症 流行病学队列（CEC）的理想定位是帮助推进本通知的目标。我们建议 利用N=1310份现有CTS生物标本，增加种族/少数民族样本的代表性， 生殖系全基因组基因分型数据库，包括伴随的暴露、表型和结果 数据;并与研究界广泛分享这些数据。2013年至2016年，两名CTS 生物库项目从参与者中收集了新的血液样本，这些样本尚未进行基因分型， 西班牙裔美国人（N=701）、非洲裔美国人（N=172）、美洲原住民（N=126）、亚裔美国人/太平洋裔美国人 岛民（N=66）或“其他/混合”（N=245）。这些参与者报告了他们自己的种族/民族以及两者的种族/民族 他们的父母。这创造了一个精确的水平，将进一步扩大未来的研究范围， CTS数据可以支持。这些参与者提供了广泛和广泛的接触，表型， 通过有效的CTS数据链接，多年的结果数据，产生详细的个人水平的癌症， 捐赠生物标本的参与者的住院和死亡结局数据。结果基因组 数据不仅可以支持癌症研究，还可以支持其他重要慢性疾病的研究（例如，心脏 疾病、糖尿病和痴呆）和医疗保健终点。CTS是CEC在数据方面的领导者 共享;自2015年以来，我们开发了新的方法、工具和基础设施来共享所有CTS信息， 资源与研究界，这些资产将有助于确保长期的成功， 项目整合基因组学研究将受益于来自少数民族和多种族的更多数据的可用性 人口，这个基于CTS的项目将有助于扩大研究界的这些资源。

PROJECT SUMMARY/ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 22-056. The goal of this funding opportunity is to increase the representation of samples and data from racial/ethnic minority populations in publicly available repositories. Including more samples from currently underrepresented racial/ethnic minority populations in these repositories is necessary but not sufficient for achieving that goal. Most human genomic research to date has focused on homogeneous European populations, as defined by genetic ancestry, and excluded multiracial individuals. Exclusion of multiracial individuals from that research increases the chances that its products—including reference panels and polygenic risk scores (PRSes)—are systematically less valid for discovery and translation in other non- European and mixed populations. This is especially worrisome in the U.S., where the number of “majority- minority” states is increasing and the multiracial populations has increased by almost 300% (from 9 million to almost 34 million) since the 2010 Census. Broader and deeper data from diverse and multiracial individuals and populations is essential for disentangling the complex interactions of race, ethnicity, ancestry, biology, and cultural constructs on health risks, outcomes, and disparities. Our California Teachers Study (CTS), a cancer epidemiology cohort (CEC), is ideally positioned to help advance the goals of this Notice. We propose to leverage N=1310 existing CTS biospecimens to increase representation of racial/ethnic minority samples in germline genome-wide genotyping data repositories with accompanying exposure, phenotype, and outcome data; and to broadly share these data with the research community. Between 2013 and 2016, two CTS biobanking projects collected new blood samples, which have not yet been genotyped, from participants who are Hispanic American (N=701), African American (N=172), Native American (N=126), Asian-American/Pacific Islander (N=66), or “other/mixed” (N=245). These participants reported their own race/ethnicity and that of both of their parents. This creates a level of precision that will further extend the future range of research that these CTS data can support. These participants have provided extensive and broad exposure, phenotype, and outcome data for years via efficient CTS data linkages that generate detailed individual-level cancer, hospitalization, and mortality outcomes data for participants who donated biospecimens. The resulting genomic data can support not just cancer research, but also research on other important chronic diseases (e.g., heart disease, diabetes, and dementia) and health-care endpoints. The CTS is a leader among CECs in data sharing; since 2015, we have developed new ways, tools, and infrastructure to share all CTS information and resources with the research community, and these assets will help ensure the long-term success of this project. Integrative genomics research will benefit from the availability of more data from minority & multiracial populations, and this CTS-based project will help expand those resources for the research community.