Develop a deeper understanding of the rare and common changes that influence susceptibility to intrahepatic cholestasis of pregnancy (ICP), a liver disease affecting pregnant women

Summary

Intrahepatic cholestasis of pregnancy (ICP) is the commonest liver disease of pregnancy and is influenced by genes, environment, and hormones. It usually affects women in the second half of pregnancy. The liver doesn’t work properly, causing a build-up of chemicals in the blood (bile acids). These chemicals can cause disease in the mother (liver damage and strong itching sensations) and can threaten the health of the unborn baby. By studying families, it has been shown the disease can be inherited, showing that changes in genetic information (DNA) play a significant role. Previous studies of Bioresource samples, DNA or saliva donated from BioResource participants, have confirmed the contribution of rare changes in two specific genes to the risk of getting ICP. Recent studies found that common genetic changes also alter the risk of getting the disease (to a smaller extent). With our new study, we want to extend our work to understand the contribution of both these types of genetic changes and to study whether this information is useful in a clinical setting. We have already used data from the Genomics England library (a separate UK resource of samples and data for genomic studies) to confirm that rare and common genetic changes can together generate the risk of getting this liver disease and we have developed ways of measuring this information. To confirm and validate these findings, we plan to use the data from the NIHR BioResource of ICP cases which we recruited as part of the rare disease project. Our overall aim is to estimate how much risk of getting ICP is caused by genetic changes, both rare and common, and to generate models to explore if this is useful information for clinicians who look after women with the disease.