GENE-FORECAST® Study

GENE-FORECAST® will test the working hypothesis that race-ancestry differences in the burden of cardiovascular disease (CVD) reflects the influence of a unique interplay between the distinct genomic variation characteristic of African-Americans (AA) and the exposome of social determinants and environmental factors that influence the pathogenesis of CVD in AA.

The specific goals of the study are:

1. To examine the associations between common or ancestry-related DNA variants and CVD risk factors (e.g. hypertension) and phenotypes (e.g. coronary artery calcification) in African-Americans (AA).
2. To examine the associations between health behaviors and social-environmental factors or CVD risk factors in AA.

The study is designed to create a cohort amenable to nested case-control analyses based on a community-based sampling frame with a target size of approximately 1800 self-identified, U.S.- born, African-American (AA) men and women (ages 21-65) to be recruited over the next 5-6 years from the metropolitan Washington D.C. area. The participant recruitment strategy will involve two complementary approaches: 1) we will contract with a well-established survey group to conduct a random-digit telephone screening survey targeting study-eligible AA that will be consented and invited to an evaluation visit in the NIH Clinical Center; and 2) we will conduct a community outreach effort to recruit participants into the Clinical Center by leveraging the engagement of community-based leaders, organizations and faith-based institutions in the area. Given the high burden of CVD among AA, this approach will yield a sample with normal individuals as well as a high proportion of AA with CVD risk factors such as obesity and hypertension that predispose to the eventual clinical signs and symptoms of CVD (e.g. heart attack and stroke).

Based on previous epidemiology studies, it is anticipated that the prevalence of clinically manifest CVD (history of angina, heart attack or stroke) will be less than 10-15 percent of the sample. All participants (either ascertained by random telephone survey or community outreach) will undergo extensive evaluation in the Clinical Center that includes: medical evaluation (e.g. anthropometrics, blood pressure), laboratory tests (e.g. lipid levels, kidney function), social determinants profiles (e.g. socioeconomic status (SES), perceived stress, discrimination, depression, perceived neighborhood characteristics), blood/urine collection for deep-sequencing based omic analyses (whole exome sequencing, and RNA-Seq), as well as testing for pre-clinical , biomarkers of the pathobiological processes of CVD or CVD phenotypes (e.g. coronary artery calcification, microalbuminuria, leukocyte telomeres, or vascular dysfunction). It is anticipated that these efforts will yield novel ancestry-related DNA variants associated with the CVD.

Accordingly, our protocol also includes a Genotype-to-Phenotype (G2P) component that re- contacts subsets of the cohort based on their genotype (e.g. APOL1 chronic kidney disease risk alleles) for a call-back visit for more in-depth phenotyping and characterization of the potential effect of the DNA variant of interest on human systems biology. In some cases family members of the proband may also be invited to participate in these G2P studies to further characterize the biological significance of these putative functional DNA variants of interest.

GENE-FORECAST® Study Flyer

You will be able to participate if you are an African-American man or woman born in the United States, between the ages of 21 and 65. You will not be able to participate if you are pregnant or breast feeding; have had a heart attack, stroke, or heart failure within the past 12 months; or were not born in the United States.

If you agree to take part in this study, there may or may not be medical benefit to you. Possible benefits include:

• Free clinical testing for your cardiovascular health profile (such as: blood pressure, cholesterol, kidney function, diabetes testing)
• Free CTA to detect blockages in the arteries feeding your heart; a test that provides some predictive value about the risk of future heart attacks.
• The results from this study will benefit the public by improving our knowledge of the relationship between genes, social factors, the environment and cardiovascular disease in African-Americans.

For potential participants meeting the GENE-FORECAST® eligibility criteria, the risks and benefits of the study will be carefully and comprehensively reviewed as part of the informed consent process. The risks of the study are rare or minor, including:

• Physical risks, such as pain or bruising as a result of the blood draw.
• Reaction to medications used for the CT/ultrasound scan.
• Radiation exposure during the CT/PET scan.
• Reaction to contrast used for CT and/or MRI scans.
• Identification of medical conditions that could require further medical treatment/follow up

Participants who need follow-up care and lack health insurance will be referred to their neighborhood community health care center such as:

• Community Clinic Inc
  www.cciweb.org
• Unity Health Care Centers
  www.unityhealthcare.org/HealthCenters.html
• Community Health Care, Inc./Upper Cardozo Health Center
  3020 14th Street, NW
  (202) 745-4313
  (202) 745-4300
• DC Family Voices
  www.familyvoices.org
  (800) 394-5694
• Howard University Hospital Family Health Center
  2339 Georgia Ave, NW
  4th Floor
  (202) 865-3250
• Mary's Center for Maternal and Child Care, Inc.
  2333 Ontario Road, NW
  Washington, D.C. 20009
  Main Phone: (202) 483-8196
  Direct Phone: (202) 483-8319
  Fax: (202) 797-2628
  info@maryscenter.org
• Washington Free Clinic
  1525 Newton Street NW
  Washington, DC 20010
  Phone: (202) 667-1106
• La Clínica del Pueblo
  2831 15th Street, NW
  Washington, DC 20009-4607
  Phone: (202) 462-4788

Nicole Plass, B.S.N., M.P.A.
Outreach & Recruitment Research Coordinator
National Institutes of Health
National Human Genome Research Institute (NHGRI)
Genomics of Metabolic, Cardiovascular, and Inflammatory Disease Branch (GMCIDB)
Cardiovascular Section
10 Center Drive, Room 7N317, MSC 1644
Bethesda, MD 20892

E-mail: GENE-FORECAST@nih.gov
Office: 844.GENE-4CT (4363-428)
Cell: 240.515.7484
Fax: 301.480.0063