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

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.887121

DOI=10.3389/fgene.2022.887121

ISSN=1664-8021

ABSTRACT=<p>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 <italic>HLA</italic> class II region (<italic>HLA-DPA1/DPB1</italic>, rs7770370, <italic>p</italic>-value = 7.71 × 10<sup>−10</sup>, OR = 0.49) with HBV chronicity. Subsequent <italic>HLA</italic> allele imputation revealed <italic>HLA-DPA1*01:03</italic> (<italic>Pc</italic> = 1.21 × 10<sup>−6</sup>, OR = 0.53), <italic>HLA-DPB1*02:01</italic> (<italic>Pc</italic> = 2.17 × 10<sup>−3</sup>, OR = 0.50), and <italic>HLA-DQB1*06:09</italic> (<italic>Pc</italic> = 2.17 × 10<sup>−2</sup>, OR = 0.07) as protective alleles, and <italic>HLA-DPA1*02:02</italic> (<italic>Pc</italic> = 6.32 × 10<sup>−5</sup>, OR = 1.63), <italic>HLA-DPB1*05:01</italic> (<italic>Pc</italic> = 1.13 × 10<sup>−4</sup>, OR = 1.72), <italic>HLA-DPB1*13:01</italic> (<italic>Pc</italic> = 4.68 × 10<sup>−2</sup>, OR = 1.60), and <italic>HLA-DQB1*03:03</italic> (<italic>Pc</italic> = 1.11 × 10<sup>−3</sup>, OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the <italic>PLSCR1</italic> (rs35766154), <italic>PDLIM5</italic> (rs62321986), <italic>SGPL1</italic> (rs144998273), and <italic>MGST1</italic> (rs1828682) loci. Among single-nucleotide polymorphisms in the <italic>PLSCR1</italic> locus, rs1061307 was identified as the primary functional variant by <italic>in silico/in vitro</italic> functional analysis. In addition to replicating the association of the <italic>HLA</italic> class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.</p>