Caitlyn Vlasschaert

Graduate Trainee, Vanderbilt University Medical Center

2 active projects

APOL1 gene mutations and Kidney Disease – controlled tier V6

We seek to identify genetic or environmental factors that modify kidney disease risk in individuals with APOL1 mutations. In the United States, African American patients who are of West-African descent have a fourfold increase in the risk of end stage…

Scientific Questions Being Studied

We seek to identify genetic or environmental factors that modify kidney disease risk in individuals with APOL1 mutations.

In the United States, African American patients who are of West-African descent have a fourfold increase in the risk of end stage kidney disease (ESKD) compared to patients of other ancestry background. Although some of this difference can be attributed to socioeconomic and clinical risk, previous studies have also identified genetic mutations in apolipoprotein L1 (APOL1) that significantly increase risk of kidney disease. The two APOL1 high-risk mutations (G1 & G2) are common as they confer resistance to lethal Trypanosoma brucei infections, which is a pathogen endemic to West Africa. While just one copy of APOL1 G1 or G2 confers protection against T. brucei rhodesiense, two copies confer increased risk of kidney disease. Although ~13% of individuals of African Americans carry two APOL1 high-risk mutations; the majority do not develop kidney disease.

Project Purpose(s)

  • Disease Focused Research (kidney disease)
  • Ancestry

Scientific Approaches

Population: Subset of AoU Data set with available genetic data that is of West African Ancestry as determined by ancestry informative genetic markers
Outcome: Kidney disease phenotypes including chronic kidney disease (CKD), end stage renal disease (ESRD) or other kidney diseases or kidney disease markers as defined in the electronic health record or other AoU datasets.
Analysis plan: We will begin by identifying which individuals have APOL1 high-risk variants G1 (rs73885319 p.S342G; rs60910145 p.I384M) and G2 (rs71785313, a 6–base pair deletion that removes amino acids N388 and Y389). We will then determine whether carrying two of these high risk variants are associated with kidney disease (recessive genetic model). We will identify whether additional genetic mutations or environmental factors modify the association between APOL1 genetic risk variants and kidney disease using multivariate logistic regression.

Anticipated Findings

The identification of genetic or environmental factors that modify kidney disease risk, might guide lifestyle modification strategies or therapeutic development for individuals with APOL1 high risk mutations.

Demographic Categories of Interest

  • Race / Ethnicity

Data Set Used

Controlled Tier

Research Team

Owner:

Duplicate of How to Work with All of Us Genomic Data (Hail - Plink)

To learn how to get started with genomic data in All of Us. I will just be following the tutorial.

Scientific Questions Being Studied

To learn how to get started with genomic data in All of Us. I will just be following the tutorial.

Project Purpose(s)

  • Educational
  • Other Purpose (Walking through this example of how to use All of Us genomic data and tools. )

Scientific Approaches

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Anticipated Findings

Not applicable - these notebooks demonstrate example analysis how to use Hail and PLINK to perform genome-wide association studies using the All of Us genomic data and phenotypic data.

Demographic Categories of Interest

This study will not center on underrepresented populations.

Data Set Used

Controlled Tier

Research Team

Owner:

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