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<p>Intrahepatic cholestasis of pregnancy, which affects 0.2–2% of pregnancies, is characterized by pruritus, increased aminotransferase activity and elevated serum bile acids. Previous studies have implicated liver-enriched genes in intrahepatic cholestasis of pregnancy. We conducted a meta-analysis of intrahepatic cholestasis of pregnancy genome-wide association studies in the FinnGen study, deCODE, Estonian Biobank, the Danish Blood Donor Study and Copenhagen Hospital Biobank with 4,738 women with prior ICP and 436,834 female controls. The analysis found 26 genome-wide significant associations of which 10 were novel. Genes in the associated loci were prioritized using lead SNP expression quantitative trait loci associations and colocalization analysis to assess potential causality. The associated loci implicate bile acid synthesis, LDL cholesterol, and lipid metabolism. Additionally, comorbidity, genetic correlation and polygenic risk score analyses further indicated a link between intrahepatic cholestasis of pregnancy and pancreatitis, suggesting shared genetic underpinnings.</p>

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Genome-wide meta-analysis identifies genetic drivers of bile acid metabolism in intrahepatic cholestasis of pregnancy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Jaakko S. Tyrmi,
  • Juha Karjalainen,
  • Samvida S. Venkatesh,
  • Clara Benoit-Pilven,
  • Susanna M. Lemmelä,
  • Søren Brunak,
  • Bitten Aagaard,
  • Mie T. Bruun,
  • Christian Erikstrup,
  • Henrik Ullum,
  • Ole B. Pedersen,
  • Karina Banasik,
  • Erik Sørensen,
  • Christina Mikkelsen,
  • Michael Schwinn,
  • Arni Sturluson,
  • Sisse R. Ostrowski,
  • Johannes Kettunen,
  • Henriette Svarre Nielsen,
  • Mette Nyegaard,
  • David Westergaard,
  • Thorunn Rafnar,
  • Patrick Sulem,
  • Kari Stefansson,
  • Priit Palta,
  • Triin Laisk,
  • Taru Tukiainen,
  • Cecilia M. Lindgren,
  • Mark Daly,
  • Aki S. Havulinna,
  • Hannele M. Laivuori

摘要

Intrahepatic cholestasis of pregnancy, which affects 0.2–2% of pregnancies, is characterized by pruritus, increased aminotransferase activity and elevated serum bile acids. Previous studies have implicated liver-enriched genes in intrahepatic cholestasis of pregnancy. We conducted a meta-analysis of intrahepatic cholestasis of pregnancy genome-wide association studies in the FinnGen study, deCODE, Estonian Biobank, the Danish Blood Donor Study and Copenhagen Hospital Biobank with 4,738 women with prior ICP and 436,834 female controls. The analysis found 26 genome-wide significant associations of which 10 were novel. Genes in the associated loci were prioritized using lead SNP expression quantitative trait loci associations and colocalization analysis to assess potential causality. The associated loci implicate bile acid synthesis, LDL cholesterol, and lipid metabolism. Additionally, comorbidity, genetic correlation and polygenic risk score analyses further indicated a link between intrahepatic cholestasis of pregnancy and pancreatitis, suggesting shared genetic underpinnings.