Familial Hypercholesterolemia
Conditions
Brief summary
This is a genomic implementation project with ancillary studies to understand the impact on patients' health and well-being of returning genomic results to them and depositing those results in the medical record.
Detailed description
Study participant DNA samples will be sequenced for 109 genes of interest along with genotyping of select polymorphisms. Genetic tests will be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab (Baylor Human Genome Sequencing Laboratory). Selected results (pathogenic/likely pathogenic) will be returned to participants by a genetic counselor and deposited into the Electronic Health Record (EHR).
Interventions
None listed
Sponsors
National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
Mayo Clinic
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Moderate to Severe Hypercholesterolemia, elevated triglycerides, or colon polyps * Resident of southeast Minnesota area * Able to provide informed consent * Current participant in the Mayo Clinic Biobank (08-007049, Cerhan PI), the Vascular Disease Biorepository (08-008355, Kullo PI), or the Study of the Genetic Determinants of Peripheral Artery Disease (PAD) (06-002911, Kullo PI) with blood derived DNA available
Exclusion criteria
* Pregnant women will be allowed to enroll in the study. This is not an interventional study and there will be no risk to the mother or neonate. Other vulnerable study populations will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant utilization of clinical resources following the return of medically actionable genetic variants. | Feb 2016-June 2020 | The EHR of study participants will be periodically reviewed beginning 6 months following the disclosure of results. EHR documented utilization of clinical resources by participants (e.g. lipid profile for cholesterol measurement, mammogram, colonoscopy, prophylactic surgery, etc.) will be reviewed to assess whether the disclosure of actionable genetic findings led to initiation of medical therapy or ordering of additional tests. Data will be manually abstracted into condition-specific REDCap questionnaires which are harmonized across multiple eMERGE Network sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of new cases detected as a result of cascade screening in the family members | Feb 2017- Dec 2020 | This outcome is being assessed as a supplemental study that includes patients with definite, probable and possible Familial Hypercholesterolemia (FH). We will compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. We will enroll 50 patients with definite FH by recruiting an additional 25 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C \>155 mg/dL (\>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case. |
| Total Expense due to disclosure of actionable variants | 4 years | The EHR will be periodically reviewed after disclosure of results to assess whether the disclosure led to initiation of medical therapy or ordering of additional tests. Measured in U.S. dollars. |
| Participant intent-to-share genetic test results | Sept 2017-June 2020 | Participants are offered pre-and-post-counseling questionnaires, provide pedigree information, and family member contact information. Questionnaires include measures of intent-to-share and barriers to sharing genetic results. |
| Number of first-degree relatives per proband and number of contacted first-degree relatives per proband | Sept 2017-Dec 2020 | The number of first-degree relatives will be assessed using patient-provided family history information. The number of contacted family members will be assessed by measuring family member response to participant contact materials. |
| Family member uptake of genetic testing | Sept 2017- Dec 2020 | Family member respondents who provide consent will be offered genetic testing. The uptake of genetic testing will be documented for each family member. |
Outcome results
None listed