Degree Name

BS

Department

Microbiology and Molecular Biology

College

Life Sciences

Defense Date

2023-03-10

Publication Date

2023-03-24

First Faculty Advisor

Mary Davis

First Faculty Reader

Brett Pickett

Honors Coordinator

David Erickson

Keywords

Multiple Sclerosis, Polygenic Risk Scores, GWAS, African American, Age of Onset

Abstract

Health disparities have been observed in autoimmune diseases such as multiple sclerosis (MS), which show that non–Hispanic black patients with MS die at an earlier age and have an increasing mortality trend compared to white MS patients.3 New genetic information shows promising results to treat genetic diseases. For example, genome-wide association studies (GWAS) are being used to calculate polygenic risk scores (PRS) which are a method used to understand disease risk. However, current PRS have been developed using GWAS that overrepresent individuals of European ancestry,4 showing that they do not equally apply to all individuals. We set out to examine if PRS could be calculated using 200 previously identified non-major histocompatibility (MHC) variants for increased MS risk in Europeans.13 We also examined if PRS using those non-MHC variants could be used to generate a PRS for African Americans.

In order to evaluate the capability of PRS to predict MS age of onset for Europeans and African Americans using non-MHC variants, we acquired de-identified electronic health records (EHR) of MS patients that had been genotyped from Vanderbilt University Medical Center BioVU. We replicated the 200 non-MHC MS risk variants in our European and African American cohorts. We then calculated PRS using the formula PRSj=∑iSi∗Gij for each cohort using the software program PRSice.8 We analyzed the efficiency of the PRS through conducting a linear regression analysis. We also identified the variants that drove this association using linear regression analysis. Our results indicated that generating a PRS by only using non-MHC MS Risk SNPs for MS age of onset in Europeans and African Americans is not sufficient for a significant calculation.

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