Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development
Jonas Ghouse, Helene Gellert‐Kristensen, Colm J. O’Rourke, Anne-Sofie Seidelin, Gudmar Thorleifsson, Garðar Sveinbjörnsson, Vinicius Tragante, Chigoziri Konkwo, Joseph Brancale, Sílvia Vilarinho, Tim Møller Eyrich, Gustav Ahlberg, Johan Skov Bundgaard, Søren A Rand, Pia R. Lundegaard, Erik Sørensen, Christina Mikkelsen, Jacob Træholt, Christian Erikstrup, Khoa Manh Dinh, Mie Topholm Bruun, Bitten Aagaard, Jakob Thaning Bay, Søren Brunak, Karina Banasik, Henrik Ullum, Triin Laisk, Reedik Mägi, Lincoln Nadauld, Kirk U. Knowlton, Stacey Knight, Lise Lotte Gluud, Kirsten Vistisen, Einar S. Björnsson, Magnús Ö. Úlfarsson, Patrick Sulem, Hilma Hólm, Ole Birger Pedersen, Sisse Rye Ostrowski, Daníel F. Guðbjartsson, Þórunn Rafnar, Kāri Stefánsson, Ulrik Lassen, Hans‐Christian Pommergaard, Jens Hillingsø, Jesper B. Andersen, Henning Bundgaard, Stefan Stender
Abstract
Background & Aims: The genetic underpinnings of hepatocellular carcinoma (HCC) remain largely unknown. Thus, we aimed to identify new genetic risk loci for HCC. Methods: We performed a genome-wide association study (GWAS) meta-analysis of 11 cohorts with validation in two independent cohorts. The identified variants were tested for effects on other hepatobiliary endpoints, and on incident HCC stratified by underlying risk factors. Mendelian randomization was used to assess the causal effects of a range of traits on the risk of HCC. Results: ) had concordant effects on HCC and biliary tract cancer. Conclusions: We identified and validated nine genetic variants associated with an increased risk of HCC development. Impact and implications: The genetic underpinnings of HCC remain largely unknown. In this genome-wide association meta-analysis totaling 6,540 cases with HCC and 2.1 million controls, we identified and validated nine genetic loci to associate with the risk of HCC. A deeper insight into genetic factors that affect the risk of HCC could improve our ability to predict and ultimately prevent or treat this deadly cancer.