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Genet."],"abstract":"<jats: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 <jats:italic>HLA<\/jats:italic> class II region (<jats:italic>HLA-DPA1\/DPB1<\/jats:italic>, rs7770370, <jats:italic>p<\/jats:italic>-value = 7.71 \u00d7 10<jats:sup>\u221210<\/jats:sup>, OR = 0.49) with HBV chronicity. Subsequent <jats:italic>HLA<\/jats:italic> allele imputation revealed <jats:italic>HLA-DPA1*01:03<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 1.21 \u00d7 10<jats:sup>\u22126<\/jats:sup>, OR = 0.53), <jats:italic>HLA-DPB1*02:01<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 2.17 \u00d7 10<jats:sup>\u22123<\/jats:sup>, OR = 0.50), and <jats:italic>HLA-DQB1*06:09<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 2.17 \u00d7 10<jats:sup>\u22122<\/jats:sup>, OR = 0.07) as protective alleles, and <jats:italic>HLA-DPA1*02:02<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 6.32 \u00d7 10<jats:sup>\u22125<\/jats:sup>, OR = 1.63), <jats:italic>HLA-DPB1*05:01<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 1.13 \u00d7 10<jats:sup>\u22124<\/jats:sup>, OR = 1.72), <jats:italic>HLA-DPB1*13:01<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 4.68 \u00d7 10<jats:sup>\u22122<\/jats:sup>, OR = 1.60), and <jats:italic>HLA-DQB1*03:03<\/jats:italic> (<jats:italic>Pc<\/jats:italic> = 1.11 \u00d7 10<jats:sup>\u22123<\/jats:sup>, OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the <jats:italic>PLSCR1<\/jats:italic> (rs35766154), <jats:italic>PDLIM5<\/jats:italic> (rs62321986), <jats:italic>SGPL1<\/jats:italic> (rs144998273), and <jats:italic>MGST1<\/jats:italic> (rs1828682) loci. Among single-nucleotide polymorphisms in the <jats:italic>PLSCR1<\/jats:italic> locus, rs1061307 was identified as the primary functional variant by <jats:italic>in silico\/in vitro<\/jats:italic> functional analysis. In addition to replicating the association of the <jats:italic>HLA<\/jats:italic> class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.<\/jats:p>","DOI":"10.3389\/fgene.2022.887121","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T05:45:38Z","timestamp":1655099138000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Genome-Wide Association Study for Chronic Hepatitis B Infection in the Thai Population"],"prefix":"10.3389","volume":"13","author":[{"given":"Saeideh","family":"Ashouri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seik-Soon","family":"Khor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Hitomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Sawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nao","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nawarat","family":"Posuwan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pisit","family":"Tangkijvanich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piyawat","family":"Komolmit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Tsuiji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vorasuk","family":"Shotelersuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Poovorawan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Mizokami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"B1","volume-title":"Affymetrix Website","year":"2022"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.3748\/wjg.v24.i30.3347","article-title":"Host Genetic Factors Affecting Hepatitis B Infection Outcomes: Insights from Genome-wide Association Studies","volume":"24","author":"Akcay","year":"2018","journal-title":"World J. 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