Research Assistant, Geisinger Clinic
1 active project
FH & ASCVD Risk
Scientific Questions Being Studied
Familial hypercholesterolemia (FH) is an inherited disorder characterized by lifelong elevated low density lipoprotein cholesterol (LDL-C) and dramatically increased risk for premature atherosclerotic cardiovascular disease (ASCVD). Genetic studies now suggest that familial hypercholesterolemia (FH) encompasses five discrete subtypes based on LDL-c levels, 1) a monogenic FH variant, 2) a high low density lipoprotein cholesterol (LDL-c) polygenic score, 3) elevated lipoprotein(a), 4) elevated LDL-c polygenic score with elevated lipoprotein(a), and 5) a positive family history without an identifiable genetic cause, or true “phenotypic FH.” The primary question of this project is: Are there differences in treatment, comorbidities, and ASCVD outcomes between FH subtypes?
- Disease Focused Research (familial hypercholesterolemia)
We plan to screen all individuals with whole genome sequences available for monogenic variants in an FH gene. We will calculate an LDL cholesterol polygenic risk score from each participant’s whole genome sequence. Using labs and measurements, we will identify individuals with an FH subtype. Additionally, we will stratify the cohort into statin treated and untreated individuals using medication data. Finally, we will use EH data to determine comorbidities and ASCVD outcomes. We will primarily use regression analyses to compare ASCVD risk in those with each FH subtype to individuals without FH.
We expect ASCVD risk to vary among FH subtypes and to be more pronounced in each of the subtypes, relative to those without FH. We also anticipate ASCVD risk and comorbidities to vary between individuals using lipid-lowering medication and those not using medication. Our findings may demonstrate the importance of considering subtypes in ASCVD risk assessment for patients with the FH phenotype.
Demographic Categories of Interest
This study will not center on underrepresented populations.
Data Set UsedControlled Tier
- Matthew Oetjens - Senior Researcher, Geisinger Clinic
- Nuha Mohammed - Research Assistant, Geisinger Clinic
- Alexander Berry - Research Associate, Geisinger Clinic
- Alex Winters - Research Associate, Geisinger Clinic
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