Coombes Brandon J, Ovsyannikova Inna G, Schaid Daniel J, Warner Nathaniel D, Poland Gregory A, Kennedy Richard B
medRxiv. 2024 Feb 27:2024.02.23.24303277. doi: 10.1101/2024.02.23.24303277.
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.
在本报告中，我们对先前发表的一项全基因组关联研究进行了随访分析，该研究涉及与腮腺炎疫苗细胞免疫反应个体差异相关的宿主基因变异。在此，我们报告一项多基因评分（PGS）分析的结果，展示常见变异如何预测腮腺炎疫苗反应。我们发现，较高的IFNγ、IL-2和TNFα多基因评分分别可预测疫苗接种后较高的IFNγ（p值 = 2×10⁻⁶）、IL-2（p = 2×10⁻⁷）和TNFα（p = 0.004）水平。疫苗接种后免疫反应的控制本质上是复杂且多基因的。我们的结果表明，基于多基因评分的方法能够更好地捕捉导致腮腺炎疫苗诱导免疫的综合遗传效应，可能比传统的单变异全基因组关联研究提供更全面的理解。这种方法在研究对其他疫苗和传染病的免疫反应的遗传控制方面可能具有广泛的用途。
