Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

中文翻译：

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人类白细胞抗原位点中侵袭性 A 组链球菌疾病和宿主遗传变异的风险升高。

侵袭性 A 群链球菌 (GAS) 疾病并不常见，但相对于其他传染病具有较高的病死率。鉴于轻度 GAS 感染无处不在，目前尚不清楚为什么健康个体偶尔会发生危及生命的感染，从而增加宿主遗传易感性的可能性。在这里，我们展示了一项病例对照研究的结果，其中包括 43 例侵袭性 GAS 病例和 1540 例对照。使用 HLA 插补和线性混合模型，我们发现 HLA-DQA1*01:03 等位基因的每个拷贝都与疾病风险增加两倍相关（优势比 2.3，95% 置信区间 1.3-4.4，P = 0.009），一种关联它与案例子集的经典 HLA 分型和使用经过验证的 HLA 数据的替代大型控制数据集进行分析保持一致。而且，我们提出这种关联是由等位基因本身而不是背景单倍型驱动的。总体而言，这一发现为进一步研究这种破坏性细菌疾病的免疫遗传学基础提供了动力。