EHR-Based Genomic Medicine Implementation

A major focus of the Atherosclerosis and Lipid Genomics Laboratory is electronic health record (EHR)-based implementation of genomic medicine.

A genome-enabled EHR is needed to:

  • Receive, store and present complex genomic information for clinical use
  • Incorporate clinical decision support to help providers practice individualized medicine
  • Provide links to relevant knowledge resources

Although adoption of electronic health records is increasing, the majority of EHR systems are not configured to manage genetic data, particularly data from whole-genome/exome sequences.

The Atherosclerosis and Lipid Genomics Lab is addressing the challenges in implementing genomic medicine using the EHR.

Related publications

Study 1: Returning results from sequencing of FH genes to individuals with elevated lipid levels

As part of the Mayo eMERGE III project, clinically actionable results relevant to familial hypercholesterolemia (FH) and hypertriglyceridemia will be returned to patients and physicians at the point of care.

This process will be followed by assessment of the subsequent patient outcomes, costs and utilization of health care resources, and behavioral and psychosocial effects.

By building on methods we developed in the eMERGE II project, our research team in the Atherosclerosis and Lipid Genomics Lab will evaluate:

  • The impact of genomic results on patient outcomes, including diagnostic and therapeutic interventions, and new-case detection in families
  • Costs and utilization of health care resources after return of results
  • Perception of genomic results, concerns about including genomic data in the EHR, worries about future employability or insurance coverage, and views regarding sharing genomic results with family members and others

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Study 2: Developing a framework to assign pathogenicity to LDLR variants

Determining potentially disease-relevant DNA variants from genome sequencing is important since false assignments of pathogenicity can have adverse consequences in clinical practice.

One of the aims of the Mayo eMERGE project is to determine which genetic variants are most likely to contribute to familial hypercholesterolemia and which should be discussed with patients and families.

Our research team is currently assessing variability in assigning pathogenicity to rare putatively functional variants identified by sequencing of LDLR.

Related publications

  • Safarova MS, Klee EW, Baudhuin LM, Winkler EM, Kluge ML, Bielinski SJ, Olson JE, Kullo IJ. Variability in Assigning Pathogenicity to Incidental Findings: Insights from LDLR Sequence Linked to the Electronic Health Record in 1013 Individuals. In review.

Study 3: Clinical trials in genomic medicine

As genetic testing becomes widely available, its use for estimating risk of common diseases is becoming of increasing scientific and public health interest.

Genome-wide association studies (GWAS) have identified multiple loci associated with coronary heart disease (CHD). The majority of these loci are associated with CHD independent of conventional risk factors and could potentially improve the accuracy of CHD risk estimates.

Several studies have investigated the association of a genetic risk score (GRS) based on multiple CHD susceptibility single-nucleotide polymorphisms (SNPs) with incident CHD events. Most of the studies reported that a GRS is associated with adverse CHD events.

Incorporating CHD genetic risk information in clinical practice may refine risk estimates and aid in prevention of CHD, concordant with recent calls to promote the practice of precision medicine. Whether disclosing genetic risk of CHD influences health-related outcomes remains unknown and clinical trials are needed to address this gap in knowledge.

Study 4: Myocardial Infarction Genes (MI-Genes) Study: Using genomic data to refine risk assessment for heart attack

Our research team conducted a clinical trial to investigate whether disclosing a genetic risk score (GRS) for coronary heart disease (CHD) leads to lowering of low-density lipoprotein cholesterol (LDL-C) levels.

The genetic risk score was incorporated into CHD risk estimates based on a conventional risk score (CRS), yielding a genetically informed risk score (+GRS). We assessed whether disclosure of genetic risk of CHD affects LDL-C levels and whether any differences were due to changes in dietary fat intake, physical activity levels or statin initiation.

We tested two hypotheses:

  • In patients randomized to receive +GRS, LDL-C levels at the end of the study period would be lower than in participants randomized to receive CRS alone
  • +GRS participants with a high GRS would have lower LDL-C levels than +GRS participants with average/low GRS and those randomized to receive CRS alone

The MI-Genes Study was conducted as an eMERGE Network genomic medicine pilot. The study investigated patient response to disclosure of genetic risk of myocardial infarction in comparison with patient response to conventional risk factors (Framingham risk score).

Genotyping results for 28 variants from 27 genes for coronary heart disease were performed and documented in the electronic medical record. Genetic counselors provided education and support for patients in the MI-Genes Study. The MI-Genes Study team developed a state-of-the art web tool for disclosure of genetic risk.

Patients participated in a series of questionnaires to determine the impact of genetic risk on social and lifestyle behaviors. Changes in health were measured through laboratory tests for lipids and self-disclosed lifestyle changes.

For more information about the MI-Genes Study, see:

Related publications

Study 5: Genetic risk score for abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is relatively prevalent in older adults. It is often asymptomatic and associated with a high mortality, up to 80 percent, due to aneurysm rupture, with poor long-term survival due to concomitant atherosclerotic cardiovascular disease (ASCVD). Previous studies also indicate a significant sex difference in terms of the prevalence, progression and outcome of the disease.

Given the important genetic component in disease development reported by previous GWAS and family-based studies, our research team in the Atherosclerosis and Lipid Genomics Lab utilized available genomic information to construct a genetic risk score of AAA to:

  • Predict aneurysm expansion
  • Assess the effect of this genetic risk score on survival in older adults with ASCVD
  • Investigate sex differences in the impact of genetic markers on aneurysm expansion

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Study 6: Pharmacogenomics eMERGE PGx Project (RIGHT PROTOCOL)

The eMERGE PGx Project involved implementation of pre-emptive pharmacogenomics across the network sites.

At Mayo Clinic, 1,013 patients underwent sequencing of 84 pharmacogenes in a Clinical Laboratory Improvement Amendments (CLIA) environment. Dr. Kullo and other investigators led the development of physician education content (AskMayoExpert) and clinical decision support (CDS) logic for three cardiovascular drugs: clopidogrel, warfarin and simvastatin.

A multidisciplinary team was involved in the creation of CDS modules. Additional and specific online PGx education was provided to physicians using web links embedded in the alerts and inboxes, as well as specific drug-gene information.

Ten CDS rules (HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, TPMT-thiopurines, CYP2D6-codeine/-tramadol/-tamoxifen, SLCO1B1-simvastatin, CYP2C19-clopidogrel, CYP2C9/VKORC-warfarin and IL28B-PEG-IFN alfa) have been approved by the Mayo Clinic PGx Task Force.

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