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在一个大型现实世界队列中,HLA遗传与SARS-CoV-2感染之间的关联

Stanley I Letovsky¹, Xia Cao², Jill A Hollenbach^3,4

¹Department of Data Science, AI, and Bioinformatics, Laboratory Corporation of America, Burlington, NC, USA. letovss@labcorp.com.

Genes and immunity

|April 24, 2025

概括

人类白细胞抗原 (HLA) 的遗传因素可能不会强烈影响SARS-CoV-2感染. 许多报道的HLA与COVID-19阳性的关联在考虑社会经济地位和暴露风险后似乎是虚假的.

科学领域:

免疫遗传学免疫遗传学
传染病流行病学传染病流行病学
基因组关联研究基因组关联研究

背景情况:

人类白细胞抗原 (HLA) 区域的遗传变异与传染病结果有关.
之前对HLA遗传学和SARS-CoV-2感染的研究由于样本大小小和混因素,得出了不确定的结果.

研究的目的:

为了调查HLA等位基因与COVID-19阳性之间的关联.
为了确定之前报告的HLA和SARS-CoV-2感染之间的关联是否在控制混变量后仍然存在.

主要方法:

对大型数据集 (419,234名受试者) 的分析,包括HLA基因型数据和COVID-19 PCR测试结果.
对非HLA因子的基线分析,随后进行多变量逻辑回归,包括单个和配对的HLA等位基因.
针对重大混因素的纠正,包括社会经济地位和暴露风险代理.

主要成果:

社会经济地位和暴露风险与所有祖先的COVID-19阳性显著相关.
最初,41个单个HLA基因组和两个HLA基因组对显示出与COVID-19阳性的显著关联.
在控制混杂因子后,只有八个单个HLA等位基因协会和两个等位基因对协会仍然具有意义.

结论:

大多数报告的HLA基因和SARS-CoV-2感染之间的关联可能是虚假的.
混因素,特别是社会经济地位,显著影响着观察到的HLA和COVID-19之间的关联.
这项研究强调了在传染病的遗传关联研究中考虑非遗传因素的重要性.

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