Despite the overwhelming focus on genetic and genomic causes of human disease over the past two decades, it has been estimated that genetics is currently known to explain only 20% and 40% of the etiology of common disease. Thus, it is becoming increasingly apparent that human disease is a consequence of both genetic susceptibility and environmental exposures. Importantly, while individuals cannot change their genetic composition, we do have the ability both personally and as a society, to influence our environment, promoting health and decreasing the risk of disease. The Personalized Environment and Genes Study (PEGS) aims to determine how the environment and gene-environment interactions can inform our understanding of human health and disease. As science has evolved, so too has the science of this project. This evolution was reflected in a change in the title of this project from the Environmental Polymorphisms Registry (EPR) to the Personalized Environment and Genes Study (PEGS) to more accurately reflect the science that can be conducted. PEGS is a unique resource because of the depth of environmental phenotyping which includes extensive information from exposome surveys, as well as whole genome sequencing on a significant number of participants in the cohort. While it is small relative to genomic cohorts, none of these have the extensive environmental data that is present in PEGS. In addition, other cohorts with deep environmental data lack the depth of genomic data that is present in PEGS. Importantly, PEGS has already provided important analytic advances that are of great interest to and can be confirmed in larger cohorts such as All of Us. The Personalized Environment and Genes Study (PEGS) aims to provide a resource for environmental health translational research by examining gene-environment interactions in health and disease. PEGS is an extension of two previous efforts where it began as a pilot study, the Environmental Polymorphisms Study (EPS; IRB# 02E9004) and was approved subsequently as a full protocol titled the Environmental Polymorphisms Registry (EPR) (IRB #04-E-N0053 and transitioned to its current ID# 04-E-0053). The EPR was envisioned as a phenotype-by-genotype registry of participants who had donated DNA samples, and who had agreed to be contacted for follow-up clinical translational studies based on their DNA genotypes. At the time, the only information available was a participant s age, sex, race, and ethnicity. Further phenotyping of a participant and/or any biospecimens obtained were investigated during a follow-up translational clinical study on participants recruited based on their genotype (hence phenotype-by-genotype) and the PEGS was the first recruit-by- genotype study at the NIH. Following a period focused on recruiting approximately 15,000 participants to enable genotyping of rare (approximately 1% minor allele frequency) single nucleotide polymorphisms (SNPs), the PEGS Consortium Project was undertaken in 2010- 2011 to examine, using the DNA of nearly 4,000 participants, approximately 700 SNPs in approximately 80 environmental response genes that work in concert with environmental exposures to elicit a phenotype. Several clinical follow-up studies, genotype-phenotype association studies, and publications have resulted from the PEGS Consortium Project. To expand phenotype information available to researchers, the Health and Exposure Questionnaire was administered between 2013-2014. In 2017, a more detailed Exposome Questionnaire which includes questions relating to the external and internal exposome was administered. This was an important resource through which to integrate exposures with genotype-phenotype association studies. Whole genome sequencing has now been performed on approximately 4700 participants who were reconsented for this purpose, as indicated above. Questionnaire data was fully adjudicated and combined in a robust and searchable database. With the increased power of the data available, the project was renamed as the Personalized Environment and Genes Study (PEGS) and rolled out in Sept. 2021. ...

Population

Convenience sample from the general population.

Brief Title

Personalized Environment and Genes Study

Official Title

Personalized Environment and Genes Study

Brief Summary

Despite the overwhelming focus on genetic and genomic causes of human disease over the past <br /> two decades, it has been estimated that genetics is currently known to explain only 20% and <br /> 40% of the etiology of common disease. Thus, it is becoming increasingly apparent that human <br /> disease is a consequence of both genetic susceptibility and environmental exposures. <br /> Importantly, while individuals cannot change their genetic composition, we do have the <br /> ability both personally and as a society, to influence our environment, promoting health and <br /> decreasing the risk of disease. The Personalized Environment and Genes Study (PEGS) aims to <br /> determine how the environment and gene-environment interactions can inform our understanding <br /> of human health and disease. As science has evolved, so too has the science of this project. <br /> This evolution was reflected in a change in the title of this project from the Environmental <br /> Polymorphisms Registry (EPR) to the Personalized Environment and Genes Study (PEGS) to more <br /> accurately reflect the science that can be conducted. PEGS is a unique resource because of <br /> the depth of environmental phenotyping which includes extensive information from exposome <br /> surveys, as well as whole genome sequencing on a significant number of participants in the <br /> cohort. While it is small relative to genomic cohorts, none of these have the extensive <br /> environmental data that is present in PEGS. In addition, other cohorts with deep <br /> environmental data lack the depth of genomic data that is present in PEGS. Importantly, PEGS <br /> has already provided important analytic advances that are of great interest to and can be <br /> confirmed in larger cohorts such as All of Us. <br /> <br /> The Personalized Environment and Genes Study (PEGS) aims to provide a resource for <br /> environmental health translational research by examining gene-environment interactions in <br /> health and disease. PEGS is an extension of two previous efforts where it began as a pilot <br /> study, the Environmental Polymorphisms Study (EPS; IRB# 02E9004) and was approved <br /> subsequently as a full protocol titled the Environmental Polymorphisms Registry (EPR) (IRB <br /> #04-E-N0053 and transitioned to its current ID# 04-E-0053). The EPR was envisioned as a <br /> phenotype-by-genotype registry of participants who had donated DNA samples, and who had <br /> agreed to be contacted for follow-up clinical translational studies based on their DNA <br /> genotypes. At the time, the only information available was a participant s age, sex, race, <br /> and ethnicity. Further phenotyping of a participant and/or any biospecimens obtained were <br /> investigated during a follow-up translational clinical study on participants recruited based <br /> on their genotype (hence phenotype-by-genotype) and the PEGS was the first recruit-by- <br /> genotype study at the NIH. Following a period focused on recruiting approximately 15,000 <br /> participants to enable genotyping of rare (approximately 1% minor allele frequency) single <br /> nucleotide polymorphisms (SNPs), the PEGS Consortium Project was undertaken in 2010- 2011 to <br /> examine, using the DNA of nearly 4,000 participants, approximately 700 SNPs in approximately <br /> 80 environmental response genes that work in concert with environmental exposures to elicit a <br /> phenotype. Several clinical follow-up studies, genotype-phenotype association studies, and <br /> publications have resulted from the PEGS Consortium Project. <br /> <br /> To expand phenotype information available to researchers, the Health and Exposure <br /> Questionnaire was administered between 2013-2014. In 2017, a more detailed Exposome <br /> Questionnaire which includes questions relating to the external and internal exposome was <br /> administered. This was an important resource through which to integrate exposures with <br /> genotype-phenotype association studies. <br /> <br /> Whole genome sequencing has now been performed on approximately 4700 participants who were <br /> reconsented for this purpose, as indicated above. Questionnaire data was fully adjudicated <br /> and combined in a robust and searchable database. With the increased power of the data <br /> available, the project was renamed as the Personalized Environment and Genes Study (PEGS) and <br /> rolled out in Sept. 2021. <br /> <br /> ...

Detailed Description

The Personalized Environment and Genes Study (PEGS) Health and Exposure Survey is designed to
collect health, family history of disease, environmental exposures and lifestyle data on PEGS
participants. PEGS was established to collect and store DNA specimens from 20,000
participants and to serve as a resource for scientists investigating genotype-driven
translational research of chronic health conditions. Under this protocol, question Health and
Exposure Survey to PEGS participants. The information used to better characterize the PEGS
population, thus making it more useful in answering research questions related to
gene-environment interactions. Data from the survey will help researchers to advance clinical
research by developing new ways of preventing, diagnosing, and treating common diseases such
as cardiovascular disease, asthma, and diabetes.

During Phases I and II, the survey was administered to PEGS participants using a modified
version of the Dillman Total Design Method (TDM) (1) for surveys. This method requires
following specific steps for survey administration that incorporate web-based, paper and
phone administration. The rationale for using the TDM was to maximize participant response
rates. As of August 2016, 9,000 PEGS participants had responded during Phase I and II
administration of the survey under protocol 12-E-0194. Efforts are ongoing to collect these
data from additional PEGS participants. During Phase III, under protocol 04-E-0053, the
survey will be distributed to new PEGS participants (i.e., those who were not enrolled in
PEGS at the time of the Phase I and II survey administrations under protocol 12-E-0194) for
self-administration at the time of enrollment and to existing PEGS participants who have not
yet completed the survey.

Investigators may select and contact participants for follow-up studies based upon health,
exposure, or disease status information; this includes responses to the PEGS Health and
Exposure Survey. Participation in follow-up studies is completely voluntary. Participants can
decide at the time they are contacted if they would like to enroll in the follow-up study.
Their decision whether or not to participate in a follow-up study will not affect their
participation in PEGS.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.