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[Preprint]. 2024 Feb 27:2024.02.23.24303277. [Version 1] doi: 10.1101/2024.02.23.24303277

Polygenic Prediction of Cellular Immune Responses to Mumps Vaccine

Brandon J Coombes, Inna G Ovsyannikova, Daniel J Schaid, Nathaniel D Warner, Gregory A Poland, Richard B Kennedy
PMCID: PMC10925362  PMID: 38464113

Abstract

In this report, we provide a follow-up analysis of a previously published genome-wide association study of host genetic variants associated with inter-individual variations in cellular immune responses to mumps vaccine. Here we report the results of a polygenic score (PGS) analysis showing how common variants can predict mumps vaccine response. We found higher PGS for IFNγ, IL-2, and TNFα were predictive of higher post-vaccine IFNγ (p-value = 2e-6), IL-2 (p = 2e-7), and TNFα (p = 0.004) levels, respectively. Control of immune responses after vaccination is complex and polygenic in nature. Our results suggest that the PGS-based approach enables better capture of the combined genetic effects that contribute to mumps vaccine-induced immunity, potentially offering a more comprehensive understanding than traditional single-variant GWAS. This approach will likely have broad utility in studying genetic control of immune responses to other vaccines and to infectious diseases.

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