Personalized Environment and Genes Study (PEGS)

个性化环境和基因研究 (PEGS)

• 批准号: 10925020
• 负责人: Janet Hall
• 金额: $ 330.29万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10925020
• 关键词: 2019-nCoV; Address; Affect; Alcohol consumption; Alcohols; Area; Asthma; Back; Behavior; Biological; Blood; COVID-19; Characteristics; Chemical Exposure; Clinical Research; Code; Cohort Studies; Collaborations; Complex; Coupled; DNA; Data; Data Collection; Dedications; Diabetes Mellitus; Diagnosis; Diet; Disease; Eligibility Determination; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Extramural Activities; Family; Family history of; Follow-Up Studies; Future; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic study; Genome; Genotype; Goals; Health; Heart Diseases; Home; Human; Individual; Infrastructure; Life; Life Cycle Stages; Life Style; Link; Longevity; Malignant Neoplasms; Measurement; Measures; Medical; Medical History; National Health and Nutrition Examination Survey; National Institute of Environmental Health Sciences; Nature; Occupational Exposure; Operative Surgical Procedures; Participant; Pathogenesis; Pharmaceutical Preparations; PhenX Toolkit; Phenotype; Physical activity; Physicians; Physiological; Population; Predisposition; Questionnaires; Recontacts; Recording of previous events; Registries; Research; Research Personnel; Resources; Risk; SARS coronavirus; Sampling; Scientist; Self Administration; Severe Acute Respiratory Syndrome; Sleep; Smoking; Smoking History; Socioeconomic Status; Stress; Study Subject; Surveys; United States National Institutes of Health; Update; Variant; Visit; Work; biobank; demographics; design; disorder risk; epigenomics; follow-up; gene environment interaction; genome sequencing; health determinants; human coronavirus; human disease; instrument; knowledge base; lifestyle data; lifestyle factors; novel coronavirus; participant enrollment; perceived stress; precision medicine; prevent; research study; response; study population; tool; translational health science; whole genome

The Environmental Polymorphisms Registry (EPR), now called Personalized Environment and Genes Study (PEGS) of over 17,000 participants provides a unique resource for a variety of studies dedicated to clarifying the interaction of genetic and environmental determinants of human health. The PEGS's subject and sample resources (blood, DNA, and other materials) can be used to examine environmental factors and gene-environment interactions in health and disease. Genotypic, phenotypic, and exposome data collected by the PEGS is used by collaborating scientists and physicians, with or without re-contact of participants, for follow-up clinical studies, to identify disease mechanisms, and to better understand individual susceptibility to disease resulting from environmental factors. In a subset of participants, DNA was subjected to whole genome sequencing (WGS) for more in-depth analysis of gene-by-environment interactions in the pathogenesis of disease. A subset of PEGS participants have also provided disease and exposure data that support a wide range of research questions. Continuing enrollment and participation of these subjects, coupled with the ability to link their data with additional, is of increasing value in this era of personalized/precision medicine. DNA samples are available to scientists to study variations in genes (polymorphisms) that may be linked to common diseases such as diabetes, heart disease, cancer, asthma and others. While many types of genes are studied as part of the EPR, the focus is on genes that may increase the risk of human disease when combined with environmental exposures (environmental response genes). Alternatively, these genes may also decrease risk of disease by protecting individuals after environmental exposures. PEGS surveys are designed to collect health, family history of disease, environmental exposures, and lifestyle data. Data from questionnaires are used to identify EPR participants who may be eligible for follow-up studies based on their health, family history, or exposures. These surveys make the EPR more useful in answering research questions related to gene-environment interactions and help researchers to develop new ways of preventing, diagnosing, and treating common diseases. PEGS Health and Exposure Survey: The PEGS Health and Exposure Survey is designed to gather health, family history of disease, environmental exposures, socioeconomic status, and lifestyle data on EPR participants. The self-administered survey, consisting of approximately 200 questions, focuses on general demographics, medical and family history, lifestyle factors, including smoking and alcohol use, and occupational exposures. Questions from validated surveys (e.g. National Health Information Survey, National Health and Nutrition Examination Survey) were used in their original format or adapted for use in the EPR. The survey is available to all PEGS participants. The information collected from 9,000 participants has been used to better characterize the EPR population, making it more useful in answering research questions related to gene-environment interactions. Data from the survey have helped researchers develop hypotheses, design follow-up studies, and select appropriate participants for participation in these follow-up studies. Exposome Survey: The PEGS Exposome Survey is designed to further enhance the EPR as a resource for NIEHS researchers and collaborators to investigate how exposures interact with an individual's unique genetic and physiologic characteristics to affect health. Approaches such as epigenomics are able to focus on the nature and timing of environmental exposures in influencing gene expression or cellular phenotypes (vs. structural changes to the genotype per se). An exposome approach offers a framework for integrating the complex world of exposures and forces impacting genome function throughout the life course. The incorporation of the exposome framework into scientific research has been limited, in part by the lack of established resources for its definition and measurement that incorporate the broader exposures encompassed by the exposome, including diet, behavior, and other endogenous and exogenous agents across life. The NIEHS PEGS Exposome Survey represents an attempt to develop a comprehensive instrument that measures an array of environmental exposures across life. In conjunction with the biorepository of DNA samples and the phenotype and lifestyle exposure data available from the earlier EPR Health and Exposure Survey, we believe the EPR Exposome Survey will be a powerful tool for exploring gene-environment interactions that can advance our understanding of complex determinants of health and disease across the life span. Questionnaire content was developed using resources such as the PhenX Toolkit, NHANES questionnaires, other NIEHS, NIH, CDC/ATSDR forms, validated scales (e.g., Cohen Perceived Stress Scale), and forms from other large cohort studies. The survey was first offered to participants beginning in early 2017, and over 3,000 participants have completed the survey to date. Administration of the survey occurs in two parts. Part A (200 questions) focuses on external exposures, including chemical and environmental exposures at home and work. Part B (200 questions) focuses on internal exposures, including medications, physical activity, stress, sleep, and diet. Data from the survey will help researchers develop hypotheses, design follow-up studies, and select appropriate participants for enrollment in the follow-up studies. Core Medical History Form: The Core Medical History Form is administered to PEGS participants visiting the NIEHS Clinical Research Unit (CRU). This form is used to collect medical history data. PEGS participants complete the Core Medical History form as part of their enrollment visit at the CRU, and update the form when they return to the CRU for research study visits. Data from the Core Medical History form is available to the PEGS to better characterize the PEGS population and enhance the PEGS as a resource for NIEHS researchers and collaborators. The Core Medical History Form includes questions on the following topics: 1) Current or Past Diseases and Medical Conditions; 2) Smoking History; 3) Alcohol History; 4) Sleep; and 5) Surgical History. The PEGS is unique in that it is a "linked" DNA registry. DNA samples are coded with personal identification numbers (PINs) that are linked back to registrants' identities, survey responses about their health and environmental exposures, and contact information. This gives researchers the ability to ask registrants to come back and participate in a wide variety of voluntary follow-up studies based on their genetic, health, or exposure profiles. We ask some PEGS participants to join other studies with the purpose of studying how genetic differences affect our bodies, or whether these differences are involved in certain conditions. We also ask some participants to join follow-up studies based on health or exposure history, responses to PEGS surveys, or other factors. This project involves research on human coronavirus, novel coronavirus, COVID-19, Severe Acute Respiratory Syndrome coronavirus disease, SARS coronavirus, SARS-coronavirus-2, SARS-cov-2, SARS-cov2, SARS-related coronavirus 2, Severe acute respiratory syndrome coronavirus 2, SARS-Associated Coronavirus, SARS-cov, or SARS-Related Coronavirus.

环境多态性登记 (EPR)，现在称为个性化环境和基因研究 (PEGS)，拥有超过 17,000 名参与者，为致力于阐明人类健康的遗传和环境决定因素的相互作用的各种研究提供了独特的资源。 PEGS 的主题和样本资源（血液、DNA 和其他材料）可用于检查健康和疾病中的环境因素以及基因-环境相互作用。 PEGS 收集的基因型、表型和暴露组数据由合作科学家和医生（无论是否再次接触参与者）用于后续临床研究，以确定疾病机制，并更好地了解个体对由以下因素引起的疾病的易感性：环境因素。对一部分参与者的 DNA 进行了全基因组测序 (WGS)，以更深入地分析疾病发病机制中基因与环境的相互作用。 PEGS 参与者的一部分还提供了支持广泛研究问题的疾病和暴露数据。这些受试者的持续注册和参与，再加上将其数据与其他数据联系起来的能力，在这个个性化/精准医学时代具有越来越大的价值。 科学家可以利用 DNA 样本来研究可能与糖尿病、心脏病、癌症、哮喘等常见疾病相关的基因变异（多态性）。虽然许多类型的基因作为 EPR 的一部分进行了研究，但重点是与环境暴露结合时可能增加人类疾病风险的基因（环境反应基因）。或者，这些基因也可以通过在环境暴露后保护个体来降低疾病风险。 PEGS 调查旨在收集健康、家族疾病史、环境暴露和生活方式数据。问卷数据用于根据 EPR 参与者的健康状况、家族史或暴露情况来确定可能有资格进行后续研究的 EPR 参与者。这些调查使 EPR 在回答与基因-环境相互作用相关的研究问题时更有用，并帮助研究人员开发预防、诊断和治疗常见疾病的新方法。 PEGS 健康和暴露调查：PEGS 健康和暴露调查旨在收集 EPR 参与者的健康、家族疾病史、环境暴露、社会经济状况和生活方式数据。这项自我管理的调查由大约 200 个问题组成，重点关注一般人口统计数据、医疗和家族史、生活方式因素，包括吸烟和饮酒以及职业暴露。经验证的调查（例如全国健康信息调查、全国健康和营养检查调查）中的问题以其原始格式使用或经过修改以用于 EPR。该调查面向所有 PEGS 参与者。从 9,000 名参与者收集的信息已被用来更好地描述 EPR 群体的特征，使其更有助于回答与基因-环境相互作用相关的研究问题。调查数据帮助研究人员提出假设、设计后续研究并选择合适的参与者参与这些后续研究。 暴露组调查：PEGS 暴露组调查旨在进一步增强 EPR，作为 NIEHS 研究人员和合作者的资源，以研究暴露如何与个体独特的遗传和生理特征相互作用以影响健康。表观基因组学等方法能够关注环境暴露影响基因表达或细胞表型（相对于基因型本身的结构变化）的性质和时间。暴露组方法提供了一个框架，用于整合整个生命过程中影响基因组功能的复杂暴露世界和力量。将暴露组框架纳入科学研究受到限制，部分原因是缺乏用于其定义和测量的既定资源，这些资源纳入了暴露组所涵盖的更广泛的暴露，包括饮食、行为以及生命中的其他内源性和外源性因素。 NIEHS PEGS 暴露组调查代表了开发一种综合工具来测量一生中一系列环境暴露的尝试。结合 DNA 样本生物存储库以及早期 EPR 健康和暴露调查提供的表型和生活方式暴露数据，我们相信 EPR 暴露组调查将成为探索基因与环境相互作用的强大工具，从而促进我们对复杂决定因素的理解整个生命周期的健康和疾病。问卷内容是使用 PhenX 工具包、NHANES 问卷、其他 NIEHS、NIH、CDC/ATSDR 表格、验证量表（例如 Cohen 感知压力量表）以及其他大型队列研究的表格等资源开发的。该调查于 2017 年初首次向参与者提供，迄今为止已有 3,000 多名参与者完成了调查。调查的管理分为两部分。 A 部分（200 个问题）重点关注外部暴露，包括家庭和工作中的化学品和环境暴露。 B 部分（200 个问题）侧重于内部暴露，包括药物、体力活动、压力、睡眠和饮食。调查数据将帮助研究人员提出假设、设计后续研究并选择合适的参与者参加后续研究。 核心病史表：核心病史表适用于访问 NIEHS 临床研究单位 (CRU) 的 PEGS 参与者。该表格用于收集病史数据。 PEGS 参与者在 CRU 登记访问期间填写核心病史表格，并在返回 CRU 进行研究访问时更新表格。 PEGS 可以使用核心病史表中的数据，以更好地描述 PEGS 人群的特征，并增强 PEGS 作为 NIEHS 研究人员和合作者的资源。核心病史表包括有关以下主题的问题： 1) 当前或过去的疾病和健康状况； 2）吸烟史； 3）酗酒史； 4）睡眠； 5) 手术史。 PEGS 的独特之处在于它是一个“链接的”DNA 登记处。 DNA 样本使用个人识别码 (PIN) 进行编码，这些识别码与注册者的身份、有关其健康和环境暴露的调查回复以及联系信息相关联。这使得研究人员能够要求注册者回来并根据他们的遗传、健康或暴露情况参与各种自愿的后续研究。 我们要求一些 PEGS 参与者加入其他研究，目的是研究遗传差异如何影响我们的身体，或者这些差异是否与某些条件有关。我们还要求一些参与者根据健康或暴露史、对 PEGS 调查的反应或其他因素参加后续研究。 该项目涉及人类冠状病毒、新型冠状病毒、COVID-19、严重急性呼吸系统综合症冠状病毒病、SARS冠状病毒、SARS-coronavirus-2、SARS-cov-2、SARS-cov2、SARS相关冠状病毒2、严重急性呼吸道疾病的研究综合征冠状病毒 2、SARS 相关冠状病毒、SARS-cov 或 SARS 相关冠状病毒。

项目成果

p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus.

p53 响应性 TLR8 SNP 增强人类对呼吸道合胞病毒的先天免疫反应。

• 发表时间: 2019
• 作者: Menendez, Daniel;Snipe, Joyce;Marzec, Jacqui;Innes, Cynthia L;Polack, Fernando P;Caballero, Mauricio T;Schurman, Shepherd H;Kleeberger, Steven R;Resnick, Michael A
• 通讯作者: Resnick, Michael A

Transethnic associations among immune-mediated diseases and single-nucleotide polymorphisms of the aryl hydrocarbon response gene ARNT and the PTPN22 immune regulatory gene.

免疫介导的疾病与芳烃反应基因 ARNT 和 PTPN22 免疫调节基因的单核苷酸多态性之间的跨种族关联。

• DOI: 10.1016/j.jaut.2019.102363
• 发表时间: 2019-11-21
• 期刊: Journal of autoimmunity
• 影响因子: 12.8
• 作者: S. Schurman;T. O’Hanlon;John A McGrath;A. Gruzdev;Arsun Bektas;Hong Xu;S. Garantziotis;D. Zeldin;F. Miller
• 通讯作者: F. Miller

TLR5 Activation Exacerbates Airway Inflammation in Asthma.

TLR5 激活会加剧哮喘气道炎症。

• 发表时间: 2020
• 影响因子: 5
• 作者: Whitehead, G S;Hussain, S;Fannin, R;Trempus, C S;Innes, C L;Schurman, S H;Cook, D N;Garantziotis, S
• 通讯作者: Garantziotis, S

UV-exposure, endogenous DNA damage, and DNA replication errors shape the spectra of genome changes in human skin.

紫外线照射、内源性 DNA 损伤和 DNA 复制错误塑造了人类皮肤基因组变化的范围。

• 发表时间: 2021
• 影响因子: 4.5
• 作者: Saini, Natalie;Giacobone, Camille K;Klimczak, Leszek J;Papas, Brian N;Burkholder, Adam B;Li, Jian;Fargo, David C;Bai, Re;Gerrish, Kevin;Innes, Cynthia L;Schurman, Shepherd H;Gordenin, Dmitry A
• 通讯作者: Gordenin, Dmitry A

Exploring the motivations of research participants who chose not to learn medically actionable secondary genetic findings about themselves.

探索选择不了解有关自己的医学上可行的二次遗传发现的研究参与者的动机。

• 发表时间: 2021-12
• 作者: Schupmann, Will;Miner, Skye A;Sullivan, Haley K;Glover, Jamie R;Hall, Janet E;Schurman, Shepherd H;Berkman, Benjamin E
• 通讯作者: Berkman, Benjamin E