Johanna Smith

Research Fellow, Mayo Clinic

1 active project

PREVENT

Our goal is to develop polygenic risk scores (PRSs) for diverse ancestry groups to ensure equitable implementation of genomic medicine and reduce the potential worsening of health disparities in the context of genomic medicine. Our focus is on atherosclerotic vascular…

Scientific Questions Being Studied

Our goal is to develop polygenic risk scores (PRSs) for diverse ancestry groups to ensure equitable implementation of genomic medicine and reduce the potential worsening of health disparities in the context of genomic medicine. Our focus is on atherosclerotic vascular disease (ASCVD) including coronary heart disease (CHD), peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), and the related risk factors: hypertension, diabetes, obesity, and hypercholesterolemia. We hypothesize that we can reduce the gap in the performance of PRSs between diverse populations by developing methods to generate PRSs for populations of diverse ancestry. All of Us will be a critical resource in this context, given that diversity is a priority in this program. We will meta-analyze the available genotype data along with similar data from dbGaP and additional datasets to improve performance of PRSs in African American, Latino, and Asian populations.

Project Purpose(s)

  • Disease Focused Research (Coronary Heart Disease)
  • Population Health
  • Methods Development
  • Control Set
  • Ancestry

Scientific Approaches

To generate PRSs for diverse ancestries, we will use data from the eMERGE consortium, Million Veteran’s Program (MVP), the All of Us (AoU) program, dbGaP, PRIMED consortium sites, the UK Biobank, and collaborations with several international groups representing Middle Eastern, South Asian, and East Asian cohorts. Our specific aims are: Aim 1. Integrate and harmonize data from heterogeneous sources to enable cross platform phenotyping and generation of PRSs for common diseases in diverse ancestry groups. Aim 2. Develop PRSs for CHD and its major risk factors (hypertension, diabetes, obesity, hypercholesterolemia) in populations of diverse ancestry. Aim 3. Develop novel statistical and computational methods to account for diverse genetic ancestry and admixture in models of polygenic risk. Aim 4. Develop ‘clinic ready’ PRSs for diverse ancestry groups by creating reference distributions of a CHD PRS and integrate it with clinical information to compute absolute risk estimates.

Anticipated Findings

We anticipate that increasing representation of diverse populations in genotyped datasets will enable the generation of more robust PRSs in these populations. We expect to advance PRS methodology for diverse populations and use novel population genetics approaches. Additionally, we will develop ‘clinic ready’ PRSs for diverse ancestry groups by creating reference distributions of a CHD PRS and integrate it with clinical information to compute absolute risk estimates.

Demographic Categories of Interest

  • Race / Ethnicity
  • Age

Data Set Used

Controlled Tier

Research Team

Owner:

Collaborators:

  • Ozan Dikilitas - Research Fellow, Mayo Clinic
  • Jacob Petrzelka - Project Personnel, Mayo Clinic
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