| Title: |
Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease |
| Authors: |
Jamialahmadi O; Mujica E; Morris L; Mancina RM; Ciociola E; Qadri SF; Maurotti S; Malvestiti F; Li-Gao R; Ronzoni L; Tavaglione F; Maude H; Allalou A; Emmanouilidou A; Vespasiani-Gentilucci U; Rosendaal FR; Yki-Järvinen H; Cebola I; Valenti L; Hoed MD; Romeo S |
| Contributors: |
O. Jamialahmadi; E. Mujica; L. Morri; R. Mancina; E. Ciociola; S. Qadri; S. Maurotti; F. Malvestiti; R. Li-Gao; L. Ronzoni; F. Tavaglione; H. Maude; A. Allalou; A. Emmanouilidou; U. Vespasiani-Gentilucci; F. Rosendaal; H. Yki-Järvinen; I. Cebola; L. Valenti; M. Hoed; S. Romeo |
| Publisher Information: |
Korean Association for the Study of the Liver |
| Publication Year: |
2025 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
CYP7A1; Gastric inhibitory polypeptide receptor; Gene-environment interaction; Genome-wide association study; MASLD; Settore MEDS-05/A - Medicina interna |
| Description: |
Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) may progress to liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. So far, genome-wide association studies explain a small fraction of MASLD heritability. Methods: We sought to identify novel genetic determinants of MASLD by exploring interactions between genetic variants and body mass index (BMI). First, we examined genome-wide interactions with BMI for circulating alanine aminotransferase (ALT) levels using UK Biobank data. For identified loci, we next examined associations with hepatic proton density fat fraction (PDFF) in 35,146 independent UK Biobank participants. Associations with PDFF were replicated in four independent European cohorts, followed by a phenome-wide association study. Finally, we used human liver epigenomic maps and CRISPR/Cas9 experiments in vitro and in vivo to functionally characterize the CYP7A1 locus. Results: Thirteen loci interact with BMI for ALT (P |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40452229; info:eu-repo/semantics/altIdentifier/wos/WOS:001619038300001; volume:31; issue:4; firstpage:1252; lastpage:1268; numberofpages:17; journal:CLINICAL AND MOLECULAR HEPATOLOGY; https://hdl.handle.net/2434/1226399 |
| DOI: |
10.3350/cmh.2025.0159 |
| Availability: |
https://hdl.handle.net/2434/1226399; https://doi.org/10.3350/cmh.2025.0159 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.B3314B24 |
| Database: |
BASE |