Smatti Maria K, Al-Sarraj Yasser A, Albagha Omar, Yassine Hadi M
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
iScience. 2023 Aug 10;26(9):107586. doi: 10.1016/j.isci.2023.107586. eCollection 2023 Sep 15.
Hepatitis E viral (HEV) infection imposes a heavy global health burden. The variability in the prevalence of serological markers of HEV infection between different ethnic groups proposes a host genetic influence. Here, we report genetic polymorphisms associated with anti-HEV antibody positivity and level using binary- and quantitative-trait genome-wide association studies (GWAS) on a population from Qatar (n = 5829). We identified a region in 12p11.1 (lead SNP: rs559856097, allele: A, p 2.3 × 10) significantly associated with anti-HEV antibodies level. This intergenic variant is located near SNORD112, a small nucleolar RNA (snoRNA). Additional gene-set and pathway enrichment analyses highlighted a strong correlation with anti-viral response-related pathways, including IFNs (alpha/beta) and interleukin-21 (IL-21) signaling. This is the first GWAS on the response to HEV infection. Further replication and functional experimentation are warranted to validate these findings.
戊型肝炎病毒（HEV）感染给全球健康带来了沉重负担。不同种族群体中HEV感染血清学标志物流行率的差异表明宿主基因存在影响。在此，我们通过对卡塔尔人群（n = 5829）进行二元和定量性状全基因组关联研究（GWAS），报告了与抗HEV抗体阳性及水平相关的基因多态性。我们在12p11.1区域（主效单核苷酸多态性：rs559856097，等位基因：A，p = 2.3×10）鉴定出一个与抗HEV抗体水平显著相关的区域。这个基因间变异位于小核仁RNA（snoRNA）SNORD112附近。额外的基因集和通路富集分析突出了其与抗病毒反应相关通路的强相关性，包括干扰素（α/β）和白细胞介素-21（IL-21）信号传导。这是首次针对HEV感染反应的GWAS。需要进一步进行重复验证和功能实验来证实这些发现。
