Genome-Wide Association Study for Chronic Hepatitis B Infection in the Thai Population

Saeideh Ashouri; Seik-Soon Khor; Yuki Hitomi; Hiromi Sawai; Nao Nishida; Masaya Sugiyama; Yosuke Kawai; Nawarat Posuwan; Pisit Tangkijvanich; Piyawat Komolmit; Makoto Tsuiji; Vorasuk Shotelersuk; Yong Poovorawan; Masashi Mizokami; Katsushi Tokunaga

doi:10.3389/fgene.2022.887121

Genome-Wide Association Study for Chronic Hepatitis B Infection in the Thai Population

Front Genet. 2022 Jun 13:13:887121. doi: 10.3389/fgene.2022.887121. eCollection 2022.

Authors

Saeideh Ashouri^{1

2}, Seik-Soon Khor^{1

2}, Yuki Hitomi³, Hiromi Sawai², Nao Nishida⁴, Masaya Sugiyama⁴, Yosuke Kawai^{1

2}, Nawarat Posuwan^{5

6}, Pisit Tangkijvanich⁷, Piyawat Komolmit^{8

9}, Makoto Tsuiji³, Vorasuk Shotelersuk¹⁰, Yong Poovorawan⁶, Masashi Mizokami⁴, Katsushi Tokunaga^{1

2}

Affiliations

¹ Genome Medical Science Project, National Center for Global Health and Medicine, Toyama, Tokyo,Japan.
² Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
⁴ Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
⁵ Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Pathum Thani, Thailand.
⁶ Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁷ Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁸ Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
⁹ Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
¹⁰ Department of Pediatrics, Center of Excellence for Medical Genomics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

To identify novel host genetic variants that predispose to hepatitis B virus (HBV) persistence, we performed the first genome-wide association study in the Thai population involving 318 cases of chronic hepatitis B and 309 healthy controls after quality control measures. We detected the genome-wide significant association of the HLA class II region (HLA-DPA1/DPB1, rs7770370, p-value = 7.71 × 10^-10, OR = 0.49) with HBV chronicity. Subsequent HLA allele imputation revealed HLA-DPA1*01:03 (Pc = 1.21 × 10^-6, OR = 0.53), HLA-DPB1*02:01 (Pc = 2.17 × 10^-3, OR = 0.50), and HLA-DQB1*06:09 (Pc = 2.17 × 10^-2, OR = 0.07) as protective alleles, and HLA-DPA1*02:02 (Pc = 6.32 × 10^-5, OR = 1.63), HLA-DPB1*05:01 (Pc = 1.13 × 10^-4, OR = 1.72), HLA-DPB1*13:01 (Pc = 4.68 × 10^-2, OR = 1.60), and HLA-DQB1*03:03 (Pc = 1.11 × 10^-3, OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the PLSCR1 (rs35766154), PDLIM5 (rs62321986), SGPL1 (rs144998273), and MGST1 (rs1828682) loci. Among single-nucleotide polymorphisms in the PLSCR1 locus, rs1061307 was identified as the primary functional variant by in silico/in vitro functional analysis. In addition to replicating the association of the HLA class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.

Keywords: GWAS; HLA; SNP; allele; chronic hepatitis B; haplotype.