{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:37:32Z","timestamp":1792543052043,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Schistosoma japonicum<\/jats:italic> infections, which lead to local inflammatory responses to schistosome eggs trapped in host tissues, can result in long-term, severe complications. The development of schistosomiasis may result from a complex interaction between the pathogenic, environmental, and host genetic components. Notably, the genetic factors that influence the development of schistosomiasis complications are poorly understood. Here we performed a genome-wide association study on multiple schistosomiasis-related phenotypes of 637 unrelated schistosomiasis patients in the Chinese population. Among three indicators of liver damage, we identified two novel, genome-wide significant single-nucleotide polymorphisms (SNPs) rs34486793 (<jats:italic>P<\/jats:italic> = 1.415 \u00d7 10<jats:sup>-8<\/jats:sup>) and rs2008259 (<jats:italic>P<\/jats:italic> = 6.78 \u00d7 10<jats:sup>-8<\/jats:sup>) at locus 14q32.2 as well as a gene, <jats:italic>PMEPA1<\/jats:italic>, at 20q13.31 (index rs62205791, <jats:italic>P<\/jats:italic> = 6.52 \u00d7 10<jats:sup>-7<\/jats:sup>). These were significantly associated with serum levels of hyaluronic acid (HA). In addition, <jats:italic>RASIP1<\/jats:italic> and <jats:italic>MAMSTR<\/jats:italic> at 19q13.33 (index rs62132778, <jats:italic>P<\/jats:italic> = 1.72 \u00d7 10<jats:sup>-7<\/jats:sup>) were significantly associated with serum levels of aspartate aminotransferase (AST), and <jats:italic>TPM1<\/jats:italic> at 15q22.2 (index rs12442303, <jats:italic>P<\/jats:italic> = 4.39 \u00d7 10<jats:sup>-7<\/jats:sup>) was significantly associated with serum levels of albumin. In schistosomiasis clinical signs, <jats:italic>ITIH4<\/jats:italic> at 3p21.1 (index rs2239548) was associated with portal vein diameter (PVD) class, an indicator of portal hypertension, and <jats:italic>OGDHL<\/jats:italic> at 10q11.23 (index rs1258172) was related to ascites grade. We also detected an increased expression of these six genes in livers of mice with severe schistosomiasis. Summary data-based Mendelian randomization analyses indicated that <jats:italic>ITIH4<\/jats:italic>, <jats:italic>PMEPA1<\/jats:italic> and <jats:italic>MAMSTR<\/jats:italic> were pleiotropically associated with PVD class, HA and AST, respectively.<\/jats:p>","DOI":"10.3389\/fcimb.2022.871545","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:40:34Z","timestamp":1649756434000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Association Study Identifies New Risk Loci for Progression of Schistosomiasis Among the Chinese Population"],"prefix":"10.3389","volume":"12","author":[{"given":"Miao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongdao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1016\/j.cell.2016.10.042","article-title":"The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease","volume":"167","author":"Astle","year":"2016","journal-title":"Cell"},{"key":"B2","first-page":"41","article-title":"Greater Resistance to Development of Severe Schistosomiasis in Brazilian Negroes","volume":"50","author":"Bina","year":"1978","journal-title":"Hum. 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