AUTHOR=Zhou Miao , Xue Chao , Wu Zhongdao , Wu Xiaoying , Li Miaoxin 

TITLE=Genome-Wide Association Study Identifies New Risk Loci for Progression of Schistosomiasis Among the Chinese Population

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.871545

DOI=10.3389/fcimb.2022.871545

ISSN=2235-2988

ABSTRACT=<p><italic>Schistosoma japonicum</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 (<italic>P</italic> = 1.415 × 10<sup>-8</sup>) and rs2008259 (<italic>P</italic> = 6.78 × 10<sup>-8</sup>) at locus 14q32.2 as well as a gene, <italic>PMEPA1</italic>, at 20q13.31 (index rs62205791, <italic>P</italic> = 6.52 × 10<sup>-7</sup>). These were significantly associated with serum levels of hyaluronic acid (HA). In addition, <italic>RASIP1</italic> and <italic>MAMSTR</italic> at 19q13.33 (index rs62132778, <italic>P</italic> = 1.72 × 10<sup>-7</sup>) were significantly associated with serum levels of aspartate aminotransferase (AST), and <italic>TPM1</italic> at 15q22.2 (index rs12442303, <italic>P</italic> = 4.39 × 10<sup>-7</sup>) was significantly associated with serum levels of albumin. In schistosomiasis clinical signs, <italic>ITIH4</italic> at 3p21.1 (index rs2239548) was associated with portal vein diameter (PVD) class, an indicator of portal hypertension, and <italic>OGDHL</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 <italic>ITIH4</italic>, <italic>PMEPA1</italic> and <italic>MAMSTR</italic> were pleiotropically associated with PVD class, HA and AST, respectively.</p>