CYP7A1 and SLC39A9 variants linked to bile acid levels and cholestasis in Chinese women

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Genetic epidemiology Published June 5, 2026 Medically reviewed June 5, 2026 Study authors: Zhang Xinyi, Li Junwei, Zhu Huanhuan, Li Linxuan, Wang Yu, Yang Meng, Wang Lin, Lan Xianmei, Wang Yi… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Interpret these genetic associations as preliminary; validation in diverse populations is needed before clinical application.

This preprint reports a genome-wide association study (GWAS) and meta-analysis conducted in a Chinese cohort of 13,357 pregnant women, investigating genetic factors influencing total bile acid (TBA) levels and intrahepatic cholestasis of pregnancy (ICP). The study identified genome-wide significant associations at CYP7A1 (rs4738680, p = 1.08 × 10^-10) and SLC39A9 (rs17107007, p = 3.46 × 10^-10) for TBA levels, and at SLC39A9 (rs17107007, p = 3.34 × 10^-10) for ICP. Pathway analysis revealed bile acid synthesis and metabolism pathways for TBA, and immune-related pathways for ICP. Integrative single-cell RNA sequencing analysis showed enrichment of TBA-associated genes in hepatocytes and ICP-associated genes in neutrophils. Mendelian randomization analysis suggested a potential causal effect of estrone on TBA levels. The authors note that underlying mechanisms remain incompletely understood, particularly in East Asian populations. While these findings may inform future research on risk prediction and targeted therapies, they are preliminary and require replication in independent cohorts.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJun 2026

PMID42076915

View Original Abstract ↓

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific 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-wide association study (GWAS) in 13,357 pregnant women from a Chinese cohort to investigate genetic determinants of TBA levels and ICP. Meta-analysis was performed by combining our data with the Shenzhen cohort. Post-GWAS analyses included pathway enrichment, integrative analysis with liver single-cell RNA sequencing (scRNA-seq) data, and Mendelian randomization (MR). We identified genome-wide significant associations at CYP7A1 (rs4738680, p = 1.08 × 10) and SLC39A9 (rs17107007, p = 3.46 × 10) for TBA, and at SLC39A9 (rs17107007, p = 3.34 × 10) for ICP. Pathway analysis highlighted bile acid synthesis and metabolism pathways for TBA and immune-related pathways for ICP. Integrative scRNA-seq analysis revealed enrichment of TBA-associated genes in hepatocytes and ICP-associated 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.