The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans
The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans
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DOI：
10.1038/s41598-020-65855-8
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发表时间：
2020-06-02
影响因子：
4.6
通讯作者：
Parks, Tom
中科院分区：
文献类型：
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作者：
Auckland, Kathryn;Mittal, Balraj;Parks, Tom
风湿性心脏病（RHD）是一种自身炎症性心脏病，最近被世界卫生组织宣布为全球健康优先事项。在这里，我们报告了一项在印度和斐济招募的1,163名南亚人（672例; 491名对照）的RHD易感性的全基因组关联研究（GWAS）。我们分析了直接获得的和插补的基因型，以及来自英国生物库研究的1,459名欧洲人（150例; 1,309名对照）的随访相关基因座。我们在南亚数据集中的人类白细胞抗原（HLA）复合物的III类区域中发现了一种新的易感性信号，该信号在欧洲人中明显重复（rs 201026476;合并比值比1.81，95%置信区间1.51-2.18，P=3.48x10（-10））。重要的是，尽管对I类和II类电极导线变体进行了调节，但该信号仍然存在（P=0.00033）。这些发现表明III类区域是RHD易感性的关键决定因素，为发病机制提供了重要的新见解，同时部分解释了早期报道的不一致性。
Rheumatic heart disease (RHD), an autoinflammatory heart disease, was recently declared a global health priority by the World Health Organization. Here we report a genome-wide association study (GWAS) of RHD susceptibility in 1,163 South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed directly obtained and imputed genotypes, and followed-up associated loci in 1,459 Europeans (150 cases; 1,309 controls) from the UK Biobank study. We identify a novel susceptibility signal in the class III region of the human leukocyte antigen (HLA) complex in the South Asian dataset that clearly replicates in the Europeans (rs201026476; combined odds ratio 1.81, 95% confidence intervals 1.51-2.18, P=3.48x10(-10)). Importantly, this signal remains despite conditioning on the lead class I and class II variants (P=0.00033). These findings suggest the class III region is a key determinant of RHD susceptibility offering important new insight into pathogenesis while partly explaining the inconsistency of earlier reports.