A1 Refereed original research article in a scientific journal
Genome-wide meta-analysis identifies genetic drivers of bile acid metabolism in intrahepatic cholestasis of pregnancy; 
Authors: Tyrmi, Jaakko S.; Karjalainen, Juha; Venkatesh, Samvida S.; Benoit-Pilven, Clara; Lemmelä, Susanna M.; Brunak, Søren; Aagaard, Bitten; Bruun, Mie T.; Erikstrup, Christian; Ullum, Henrik; Pedersen, Ole B.; Banasik, Karina; Sørensen, Erik; Mikkelsen, Christina; Schwinn, Michael; Sturluson, Arni; Ostrowski, Sisse R.; FinnGen; Estonian Biobank research team; DBDS Genomic Consortium; Kettunen, Johannes; Nielsen, Henriette Svarre; Nyegaard, Mette; Westergaard, David; Rafnar, Thorunn; Sulem, Patrick; Stefansson, Kari; Palta, Priit; Laisk, Triin; Tukiainen, Taru; Lindgren, Cecilia M.; Daly, Mark; Havulinna, Aki S.; Laivuori, Hannele M.
Publisher: Springer Science and Business Media LLC
Publication year: 2026
Journal: Nature Communications
Article number: 6778
Volume: 17
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-026-73122-z
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://doi.org/10.1038/s41467-026-73122-z
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/526991431
Self-archived copy's licence: CC BY NC ND
Self-archived copy's version: Publisher`s PDF
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.
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Funding information in the publication:
We want to acknowledge the participants and investigators of the FinnGen study. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis AG, and Boehringer Ingelheim International GmbH. Following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta), Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki/) and Arctic Biobank (https://www.oulu.fi/en/university/faculties-and-units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank). All Finnish Biobanks are members of BBMRI.fi infrastructure (https://www.bbmri-eric.eu/national-nodes/finland/). Finnish Biobank Cooperative -FINBB (https://finbb.fi/) is the coordinator of BBMRI-ERIC operations in Finland. The Finnish biobank data can be accessed through the Fingenious® services (https://site.fingenious.fi/en/) managed by FINBB. Full list of FinnGen investigators is provided in Supplementary Data 15. We thank the participants of the DBDS Genomic Consortium for their contributions. List of DBDS Genomic Consortium members is provided in Supplementary Data 16. We want to acknowledge the participants of the Estonian Biobank for their contributions. The Estonian Genome Center analyses were carried out in the High Performance Computing Center, University of Tartu. This work was supported by the Estonian Research Council grant PRG1291 (Systematic phenome-wide search for genetic modulators in health and disease) and Ministry of Education and Research Centres of Excellence grant TK214 (Centre of Excellence for Personalized Medicine). The Estonian Biobank Research Team was responsible for data collection, genotyping, quality control and imputation. List of Estonian Biobank Research Team is provided in Supplementary Data 17. The authors declare no relevant funding.
