Genomic Study Identifies Risk Regions for Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) affects 0.2–2% of pregnancies and typically arises after 30 weeks, presenting with intense itching of the palms and soles. Diagnosis is confirmed by elevated liver enzymes and increased serum bile acids, and the condition is linked to higher risks of preterm birth and stillbirth. Although genetic susceptibility has been suspected, the underlying mechanisms have been unclear. New findings demonstrate that large-scale human genetic analyses have identified multiple regions associated with ICP.

Tampere University led an international genome-wide meta-analysis that combined genetic data from more than 4,700 women with a history of ICP and over 436,000 control women from Finland, Iceland, Estonia and Denmark. The study identified 26 genetic regions associated with ICP, including 10 not previously reported. Genes within these regions influence hepatic handling of bile acids, fats and cholesterol, aligning ICP susceptibility with broader disturbances in liver metabolism during pregnancy-related hormonal changes.

The investigators also examined clinical associations beyond pregnancy. Women with prior ICP showed an increased risk of hepatobiliary disorders, including fatty liver disease, gallstones and inflammation of the bile ducts, as well as higher rates of certain autoimmune diseases such as Crohn’s disease, thyroid disorders and type 2 diabetes. Analyses further suggested a possible shared genetic basis between ICP and pancreatitis.

The findings were published in Nature Communications on May 25, 2026. According to the study authors, the results hold promise for identifying at‑risk groups, improving diagnosis and treatment, and supporting the early identification of related conditions. The work involved researchers affiliated with Tampere University and the University of Oulu.

"Our analyses also suggested a possible shared genetic basis between ICP and pancreatitis, which is inflammation of the pancreas, meaning that the same genetic susceptibility may increase the risk of both conditions. This is a new discovery that, to our knowledge, has not been reported previously. However, further studies are needed to better understand this connection," said Jaakko Tyrmi, postdoctoral research fellow at Tampere University and the University of Oulu.

Related Links
Tampere University