Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
Department of Renal Medicine, University College London, London, UK.
Nat Commun. 2022 Aug 17;13(1):4840. doi: 10.1038/s41467-022-29931-z.
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
妊娠期肝内胆汁淤积症（ICP）是一种妊娠特有的肝脏疾病，影响 0.5-2%的妊娠。大多数病例在妊娠晚期出现瘙痒、血清胆汁酸升高和血清肝酶异常。ICP 与不良结局的风险增加有关，包括自发性早产和死胎。虽然影响肝胆转运体的罕见突变有助于 ICP 的发病机制，但迄今为止，ICP 中常见遗传变异的作用尚未得到系统描述。在这里，我们对包括 1138 例病例和 153642 例对照在内的三项研究中的 ICP 进行全基因组关联研究（GWAS）和荟萃分析。有 11 个位点达到全基因组显著水平，并进一步通过功能基因组学方法进行了研究和精细映射。我们的研究结果指出，富含肝脏的基因和肝脏特异性顺式调控元件中的常见序列变异是导致 ICP 易感性的机制。
