The Impact of Personal Genomics (PGen) Study (R01 HG005092)

Principal Investigators: Robert C. Green and Scott Roberts

The rapid identification of genetic risk factors for common, complex diseases poses great opportunities and challenges for public health. Genetic information is increasingly being utilized as part of commercial efforts, including personal genomic testing, to provide consumers with genetic risk information related to common diseases. Few empirical data have been gathered to understand the characteristics of consumers, the psychological, behavioral, and health impact, and the ethical, legal, and social issues associated with personal genomic testing services. 

In the NIH-funded Impact of Personal Genomics (PGen) Study, we surveyed consumers of two U.S. companies that provide personal genetic testing—23andMe and Pathway Genomics—to determine consumers’ reactions to genetic risk information for common diseases of interest, including heart disease, diabetes, Alzheimer’s disease, arthritis, and breast, colon, lung, and prostate cancers. This study utilizes third-party data collection and analysis procedures to enable an independent consideration of the benefits and risks of personal genomic testing. With participants’ permission, 23andMe and Pathway Genomics also provided researchers with individual-level genetic risk information, which was subsequently linked to participants' longitudinal survey responses. A total of 1,648 participants provided survey data at baseline, of which 1,489 were eligible for follow-up. Of these, survey data was collected from 1,046 participants at 2-week follow-up, and 1,042 participants at 6-month follow-up. Over 900 participants completed all 3 surveys, and 1,155 participants completed at least one follow-up survey, resulting in a large and diverse cohort for longitudinal investigations into the impact of personal genomic testing.

To implement this research, we have assembled an interdisciplinary team of experts with backgrounds in medicine, genetic testing policy and practice, health communication, genetic counseling, health psychology, health law, bioethics, and web survey design. Our aims are as follows: 1) to describe who seeks personal genomic testing and why, by collecting information on demographics, motivations for seeking testing, and understanding of genetics; 2) to describe the impact of personal genomic testing, including psychological impact, risk perceptions and comprehension, and personal utility of services; and 3) to assess what consumers do with their genetic information in the domains of health behaviors, insurance changes, information seeking, and communication with family and health care providers. This study will produce results that can be translated into recommendations to guide practice and policy in this rapidly emerging area.

Opportunities to support the The PGen Study are available.

Please visit the G2P Giving Page to learn more!

Please direct any further inquiries regarding the Impact of Personal Genomics (PGen) Study to Sheila Sutti.

REVEAL-SCAN: Risk Evaluation and Education of Alzheimer's Disease - the Study of Communicating Amyloid Neuroimaging (RF1 AG047866)

Principal Investigators: Robert C. Green and Jason Karlawish

Co-Principal Investigators: J. Scott Roberts and Kathleen Welsh-Bohmer

Alzheimer’s disease (AD) clinical trials have traditionally tested potential treatments for individuals with symptoms of dementia, but the discovery of AD biomarkers has dramatically altered this approach. Trials such as the Anti-Amyloid in Asymptomatic Alzheimer’s Study, or A4 Study, are now focusing on enrolling cognitively normal participants who have biomarkers suggestive of “preclinical AD,” in order to delay the onset of cognitive impairments. This goal presents two questions of critical importance to both the validity and safety of these trials, and the successful translation of their results into clinical practice: (1) Will individuals’ knowledge of their biomarker status bias cognitive outcomes? (2) Will such knowledge prompt beneficial behavior changes or cause adverse psychological and social consequences?

REVEAL-SCAN: Risk Evaluation and and Education of Alzheimer's Disease - the Study of Communicating Amyloid Neuroimaging (RF1 AG047866) is the first multi-site, randomized clinical trial to examine the impact of learning amyloid imaging results in cognitively normal individuals, and its goal is to answer these questions.

If simply learning that one is biomarker positive causes a person to perform worse on cognitive testing, then primary outcomes data of AD trials may not be valid. Moreover, since amyloid imaging received FDA approval for use in cognitively impaired individuals, our preliminary studies show that clinical investigators want guidance on whether and how to disclose amyloid imaging results, not only to these individuals, but also to cognitively normal older individuals.

In this study, risk communication protocols will be developed and implemented for communicating amyloid PET brain imaging results. Then, 270 cognitively normal individuals (approximately 25% African American), aged 65-80, will be recruited and randomized to receive their amyloid scan results or not, resulting in subjects whose scan results are disclosed or not and subjects whose scans are amyloid positive or not. Apolipoprotein (APOE) genotyping with oversampling of ε4+ individuals will be used to enrich the enrollment sample, such that roughly half of those scanned will be amyloid positive and half will be amyloid negative. The primary neuropsychological outcome will be the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) and the primary psychological outcome for psychological distress will be the Impact of Events Scale (IES).

The core team that will conduct this project has worked together for over ten years on the NIH-funded REVEAL Study (R01 HG02213) trials that have studied risk estimation, risk communication and the disclosure of APOE genotype for risk of AD. Our aims are as follows: 1) to determine whether disclosure of elevated brain amyloid will bias ADCS-PACC test results; 2) to determine whether disclosure of elevated brain amyloid will cause psychological distress; and 3) to explore how learning amyloid imaging disclosure will impact preventative health behaviors, advance planning for health (e.g. long-term care insurance decisions) and well-being (e.g. stigma, quality of life and relationships).

REVEAL-SCAN is currently enrolling participants. For a downloadable brochure, please click "here". To learn more about this study or if you are interested in participating, please contact Sheila Sutti, MS, CGC, Genetic Counselor and Project Manager for the REVEAL-SCAN Study.

The Personal Genome Sequencing Outcomes (PeopleSeq) Consortium

Principal Investigator: Robert C. Green 

Genomic sequencing, including whole genome sequencing (WGS) and whole exome sequencing (WES), are available to and being utilized by physicians and their patients in both research and clinical settings. Thousands of patients have received genomic sequencing with the goal of establishing diagnoses for rare or genetically heterogeneous disorders, a process that previously would have required multiple individual genetic tests performed over long periods of time and at a substantial cost. Beyond its diagnostic utility, there is hope that genomic sequencing, when performed in ostensibly healthy individuals, will be a key tool in the development of a more personalized and preventative model of medical care.

The use of genomic sequencing in healthy populations to screen for disease variants is conceptually very different from anything practiced today in medical genetics. Instead of using genomic technology in the hopes of identifying a cause for a specific condition, genomic sequencing in healthy individuals would follow a model of "predispositional" genomic testing. Unlike many epidemiologic studies in genetics and genomics, this model envisions results being returned in a readily understandable report to patients and their clinicians as part of the patient’s regular care. Identification of rare genetic variants associated with significantly increased risks for certain cardiac events or cancers could allow for preemptive clinical management and prevention of disease. Genomic sequencing of healthy individuals could grow to resemble current population-based preventative screening measures, such as newborn screening or the use of colonoscopy after age 50, which have been integrated into clinical practice to identify uncommon diseases.

Despite the promise of genomic sequencing for personalized medicine, there remain significant challenges and concerns that must be addressed. Some consider the utilization of genomic sequencing in healthy individuals to be controversial; the short and long-term outcomes of providing genomic sequencing information to healthy adults are not known and are of great interest.

In the PeopleSeq Consortium, we are conducting a longitudinal study of healthy adults by surveying those who plan to, or have already received, their own genomic sequence information through various commercial and research avenues that follow different return of results models. The PeopleSeq Consortium enables us to collect valuable empirical data on the medical, behavioral and economic impact of performing genomic sequencing in healthy adults. To accomplish this, we have drawn upon our prior experience in designing and implementing rigorous studies of the outcomes of genetic testing and results disclosure, including the Impact of Personal Genomics (PGen) Study and the MedSeq Project.

To view preliminary data from the PeopleSeq Consortium, please click here and here.

To learn more about the study please contact Wendi Betting, Project Manager for the PeopleSeq Consortium.

Members and Participating Institutes in the PeopleSeq Consortium:

Brigham and Women’s Hospital
Robert Green
Wendi Betting
Daiva Nielsen

Middlebury College
Michael Linderman

Illumina, Inc.
Molly McGinniss
Erica Ramos
Jamie Esposito

Harvard Personal Genome Project
George Church
Madeleine Ball

Icahn School of Medicine at Mount Sinai
Eric Schadt

Baylor College of Medicine
Amy McGuire
Thomas Caskey
Hayley Peoples
Stacey Pereira

Invitae, Inc.
Ed Esplin
Eden Haverfield

Institute of Systems Biology
Lee Hood
Jennifer Lovejoy
Nathan Price

Nevada Institute of Personalized Medicine
Martin Schiller
Jenica Abrudan
Michael Nasiak
Qing Wu

University of Vermont
Debra Leonard

SoundRocket
Scott Crawford
Rob Young
Julie Smith

HudsonAlpha Institute of Biotechnology
Candice Finnila
Thomas May

Consultants
Nathaniel Pearson
Scott Roberts
Saskia Sanderson