Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study.
BACKGROUND
Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown. We describe design of the Myocardial Infarction Genes (MI-GENES) Study, a randomized clinical trial to assess whether disclosing a GRS for coronary heart disease (CHD) leads to lowering of low-density lipoprotein cholesterol (LDL-C) levels.


METHODS
We performed an initial screening genotyping of 28 CHD susceptibility single-nucleotide polymorphisms (SNPs) that are not associated with blood pressure or lipid levels, in 1000 individuals from Olmsted County, Minnesota who were participants in the Mayo Clinic BioBank and met eligibility criteria. We calculated GRS based on 28 SNPs and will enroll 110 patients each in two CHD genomic risk categories: high (GRS ≥1.1), and average/low (GRS <1.1). The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record. Participants will undergo a blood draw and return 6-10 weeks later (Visit 2) once genotyping is completed and a GRS calculated. At this visit, patients will be randomized (1:1) to receive CHD risk estimates from a genetic counselor based on a conventional risk score (CRS) vs. GRS, followed by shared decision making with a physician regarding statin use. Three and six months following the disclosure of CHD risk, participants will return for measurement of fasting lipid levels and assessment of changes in dietary fat intake and physical activity levels. Psychosocial measures will be assessed at baseline and after disclosure of CHD risk.


CONCLUSIONS
The proposed trial will provide insights into the clinical utility of genetic testing for CHD risk assessment.


BACKGROUND
ClinicalTrials.gov registration number: NCT01936675 .
From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Kullo.Iftikhar@mayo.edu.
Iftikhar J
IJ
Kullo
From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Hayan
H
Jouni
From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Janet E
JE
Olson
From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Victor M
VM
Montori
From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Kent R
KR
Bailey
D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D030881:Disclosure; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
D008078:Cholesterol, LDL; D004041:Dietary Fats