Abstract
BackgroundWhether 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 designWe 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.DiscussionThe proposed trial will provide insights into the clinical utility of genetic testing for CHD risk assessment.Clinical trial registrationClinicalTrials.gov registration number: NCT01936675.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0122-0) contains supplementary material, which is available to authorized users.
Highlights
Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown
Overall study design To maximize information yield from the study, we performed an initial screening genotyping of 28 coronary heart disease (CHD) susceptibility Singlenucleotide polymorphism (SNP) that are not associated with blood pressure (BP) or lipid levels, in 1000 individuals from Olmsted County who were participants in the Mayo Clinic BioBank and met the eligibility criteria
Of these 2026 individuals, a random subset of 1000 was genotyped for the 28 SNPs associated with CHD independent of blood pressure and lipid levels to calculate a GRS for each individual
Summary
Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown. In one of the first genome-wide association studies (GWAS) [2], common genetic variants in the 9p21 region were associated with coronary heart disease (CHD) with an odds ratio of 1.22 per risk allele. Subsequent meta-analyses in largely European ancestry populations identified additional loci of modest effect sizes associated with CHD [3,4]. The majority of these loci are associated with CHD independent of conventional risk factors and could potentially improve the accuracy of CHD risk estimates. Whether disclosing results of genetic testing for CHD risk influences relevant clinical outcomes is Several studies have reported that a genetic risk score (GRS) based on multiple CHD susceptibility single-nucleotide polymorphisms (SNPs) provides incremental information for CHD risk estimation [5,6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
