Genome-wide association study identifies several loci for HEV seropositivity

Maria K Smatti; Yasser A Al-Sarraj; Omar Albagha; Hadi M Yassine

doi:10.1016/j.isci.2023.107586

Genome-wide association study identifies several loci for HEV seropositivity

iScience. 2023 Aug 10;26(9):107586. doi: 10.1016/j.isci.2023.107586. eCollection 2023 Sep 15.

Authors

Maria K Smatti¹, Yasser A Al-Sarraj^{1

2}, Omar Albagha^{1

3}, Hadi M Yassine⁴

Affiliations

¹ College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
² Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
³ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴ Biomedical Research Center, Qatar University, Doha, Qatar.

Abstract

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^-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.

Keywords: Association analysis; Immune response; Quantitative genetics; Virology.