Impact of genetic variants linked to liver fat and liver volume on MRI-mapped body composition
Liver fat and liver volume are common metabolic traits with a strong genetic component, yet the extent to which they exert organ-specific <i>vs.</i> systemic effects remains poorly defined. By integrating genome-wide association analyses and high-resolution neck-to-knee magnetic resonance imaging data through the Imiomics framework, this study reveals distinct genetic architectures for liver fat and liver volume, including sex-specific effects. These findings provide new insights into the biological, organ-level, tissue-specific, and systemic characteristics of steatotic liver disease and its genetic determinants. The results may inform the development of precision imaging genetic approaches, biomarker discovery, and stratified risk assessment strategies, while reinforcing the importance of incorporating sex-specific analyses in future research and clinical applications.
Authors
- Sergi Sayols-Baixeras (ORCID: https://orcid.org/0000-0002-1181-6262)
- Beatrice Kennedy (ORCID: https://orcid.org/0000-0002-0066-4814)
- Tove Fall (ORCID: https://orcid.org/0000-0003-2071-5866)
- Ulf Hammar (ORCID: https://orcid.org/0000-0001-8367-5000)
- Lars Lind (ORCID: https://orcid.org/0000-0003-2335-8542)
- Robin Strand (ORCID: https://orcid.org/0000-0001-7764-1787)
- Andrés Martínez Mora (ORCID: https://orcid.org/0000-0002-7293-8220)
- Håkan Åhlström (ORCID: https://orcid.org/0000-0002-8701-969X)
- Nouman Ahmad (ORCID: https://orcid.org/0000-0003-0202-9205)
- Jan W. Eriksson (ORCID: https://orcid.org/0000-0002-2639-9481)
- Taro Langner
- Jenny C. Censin (ORCID: https://orcid.org/0000-0001-6625-6074)
- Tuomas O. Kilpeläinen (ORCID: https://orcid.org/0000-0002-8349-3028)
- Germán D. Carrasquilla (ORCID: https://orcid.org/0000-0002-7147-9421)
- Koen F. Dekkers (ORCID: https://orcid.org/0000-0002-4074-7235)
- Joel Kullberg (ORCID: https://orcid.org/0000-0001-8205-7569)
- Shafqat Ahmad (ORCID: https://orcid.org/0000-0002-3873-7943)
- Uwe Menzel
- Diem Thi Nguyen (ORCID: https://orcid.org/0000-0002-9680-5772)
- Filip Malmberg (ORCID: https://orcid.org/0000-0002-4980-2755)
- María J Romero-Lado (ORCID: https://orcid.org/0009-0001-9500-3292)
Institutions
- Broad Institute (US)
- Uppsala University (SE)
- University of Copenhagen (DK)
- Brigham and Women's Hospital (US)
- Södertörn University (SE)
- Centre for Human Genetics (GB)
- Harvard University (US)
- Novo Nordisk Foundation (DK)
- Instituto de Salud Carlos III (ES)
- Foundation Center (US)
- University of Oxford (GB)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Novo Nordisk (United States) (US)
- Antaros Medical (Sweden) (SE)
- Health Data Research UK (GB)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101468
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Brigham and Women's Hospital
- Broad Institute
- University of Oxford
- European Commission
- Svenska Forskningsrådet Formas
- Hjärt-Lungfonden
- Novo Nordisk
- Vetenskapsrådet
- Uppsala Universitet
- Faculty of Health and Medical Sciences, University of Western Australia
- Novo Nordisk Fonden
- Novo Nordisk Foundation Center for Basic Metabolic Research
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares
- Medical Research Council
- Instituto de Salud Carlos III
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
- Uppsala Multidisciplinary Center for Advanced Computational Science