{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:02:56Z","timestamp":1779793376101,"version":"3.53.1"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy\u2010specific liver disorder characterized by elevated total bile acid (TBA) levels, leading to adverse maternal and fetal outcomes. While genetic factors contribute to ICP and bile acid metabolism, the underlying mechanisms remain incompletely understood, particularly in East Asian populations. We conducted a genome\u2010wide association study (GWAS) in 13,357 pregnant women from a Chinese cohort to investigate genetic determinants of TBA levels and ICP. Meta\u2010analysis was performed by combining our data with the Shenzhen cohort. Post\u2010GWAS analyses included pathway enrichment, integrative analysis with liver single\u2010cell RNA sequencing (scRNA\u2010seq) data, and Mendelian randomization (MR). We identified genome\u2010wide significant associations at\n                    <jats:italic>CYP7A1<\/jats:italic>\n                    (rs4738680,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.08\u2009\u00d7\u200910\n                    <jats:sup>\u221210<\/jats:sup>\n                    ) and\n                    <jats:italic>SLC39A9<\/jats:italic>\n                    (rs17107007,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.46\u2009\u00d7\u200910\n                    <jats:sup>\u221228<\/jats:sup>\n                    ) for TBA, and at\n                    <jats:italic>SLC39A9<\/jats:italic>\n                    (rs17107007,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.34\u2009\u00d7\u200910\n                    <jats:sup>\u221216<\/jats:sup>\n                    ) for ICP. Pathway analysis highlighted bile acid synthesis and metabolism pathways for TBA and immune\u2010related pathways for ICP. Integrative scRNA\u2010seq analysis revealed enrichment of TBA\u2010associated genes in hepatocytes and ICP\u2010associated genes in neutrophils. MR analysis suggested a potential causal effect of estrone on TBA levels. Our findings provide novel insights into the genetic architecture of TBA and ICP, emphasizing the roles of bile acid metabolism in hepatocytes and immune dysregulation in ICP pathogenesis. The identified genetic loci and pathways may inform future research on risk prediction and targeted therapies for ICP.\n                  <\/jats:p>","DOI":"10.1002\/gepi.70040","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:44:14Z","timestamp":1777877054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared and Distinct Genetic Factors Underlying Bile Acid Regulation and Intrahepatic Cholestasis of Pregnancy"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5472-3568","authenticated-orcid":false,"given":"Xinyi","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences Beijing China"},{"name":"Shenzhen Key Laboratory of Transomics Biotechnologies, BGI Research Shenzhen 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