Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study

Iftikhar J Kullo, Hayan Jouni, Janet E Olson, Victor M Montori, Kent R Bailey, Iftikhar J Kullo, Hayan Jouni, Janet E Olson, Victor M Montori, Kent R Bailey

Abstract

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 and design: 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.

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

Clinical trial registration: ClinicalTrials.gov registration number: NCT01936675 .

Figures

Fig. 1
Fig. 1
Flow Diagram of the Proposed Clinical Trial. A flow diagram illustrating the design of the MI-GENES study. A total of 2026 individuals from the Mayo BioBank met the eligibility criteria. Among those 2026, a random sample of 1000 individuals was sent for screening genotyping. A total of 968 individuals had valid screening genotyping results. Recruitment was based on screening genotyping results in order to achieve the targeted enrollment goals of ~110 individuals with high GRS (≥1.1) and ~110 with average/low GRS (

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