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The role of liver f...
The role of liver fat in cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
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- van der Meer, Dennis (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
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- Gurholt, Tiril P. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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- Sønderby, Ida E. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo
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- Shadrin, Alexey A. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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- Hindley, Guy (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Psychosis Studies, Institute of Psychiatry, Psychology and Neurosciences, King’s College London, United Kingdom
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- Rahman, Zillur (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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- de Lange, Ann-Marie G. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; LREN, Centre for Research in Neurosciences, Dept. of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; Dept. of Psychiatry, University of Oxford, Oxford, UK
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- Frei, Oleksandr (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway
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- Dahlqvist Leinhard, Olof, 1978- (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV,AMRA Medical, Linköping, Sweden
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- Linge, Jennifer (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,AMRA Medical, Linköping, Sweden
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- Simon, Rozalyn, 1979- (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV
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- Westlye, Lars T. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo; Department of Psychology, University of Oslo, Oslo, Norway
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- Halvorsen, Sigrun (author)
- Department of Cardiology, Oslo University Hospital Ullevål, and University of Oslo, Oslo, Norway
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- Dale, Anders M. (author)
- Center for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA 92037, USA
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- Karlsen, Tom H. (author)
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
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- Kaufmann, Tobias (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry and Psychotherapy, University of Tübingen, Germany
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- Andreassen, Ole A. (author)
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo
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(creator_code:org_t)
- Cold Spring Harbor Laboratory, 2022
- English.
- Related links:
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https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://www.biorxiv....
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Abstract
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- Background & AimsObesity and associated morbidities, metabolic associated liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting the first genome-wide association study (GWAS) of these MRI-derived measures.MethodsWe ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 34,036 White European UK Biobank participants (mean age of 64.5 years, 51.5% female).ResultsThrough multivariate analysis, we discovered 108 loci with distributed effects across the body composition measures and 256 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h2=.25 vs. .16, p=1.4×10−6). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (rg=.48, p=1.6×10−22).ConclusionsThese findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Publication and Content Type
- vet (subject category)
- ovr (subject category)
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- By the author/editor
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van der Meer, De ...
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Gurholt, Tiril P ...
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Sønderby, Ida E.
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Shadrin, Alexey ...
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Hindley, Guy
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Rahman, Zillur
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de Lange, Ann-Ma ...
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Frei, Oleksandr
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Dahlqvist Leinha ...
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Linge, Jennifer
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Simon, Rozalyn, ...
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Westlye, Lars T.
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Halvorsen, Sigru ...
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Dale, Anders M.
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Karlsen, Tom H.
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Kaufmann, Tobias
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Andreassen, Ole ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- By the university
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Linköping University