The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition.

Autor: van der Meer D; 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. d.v.d.meer@medisin.uio.no.; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. d.v.d.meer@medisin.uio.no., Gurholt TP; 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., Sønderby IE; 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, Oslo, Norway., Shadrin AA; 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., Hindley G; 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, London, UK., Rahman Z; 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., de Lange AG; 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., Frei O; 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., Leinhard OD; AMRA Medical, Linköping, Sweden.; Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden., Linge J; AMRA Medical, Linköping, Sweden.; Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden., Simon R; Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden., Beck D; 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 Psychology, University of Oslo, Oslo, Norway.; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway., Westlye LT; 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, Oslo, Norway.; Department of Psychology, University of Oslo, Oslo, Norway., Halvorsen S; Department of Cardiology, Oslo University Hospital Ullevål, and University of Oslo, Oslo, Norway., Dale AM; Center for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA, 92037, USA., Karlsen TH; 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., Kaufmann T; 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, Tübingen, Germany., Andreassen OA; 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, Oslo, Norway.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Nov 19; Vol. 5 (1), pp. 1271. Date of Electronic Publication: 2022 Nov 19.
DOI: 10.1038/s42003-022-04237-4
Abstrakt: Obesity and associated morbidities, metabolic associated fatty 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 genome-wide association studies (GWAS) of these MRI-derived measures. We ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 33,588 White European UK Biobank participants (mean age of 64.5 years, 51.4% female). Through multivariate analysis, we discovered 100 loci with distributed effects across the body composition measures and 241 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 (h 2  = .25 vs. .13, p = 1.8x10 -7 ). 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 (r g  = .49, p = 2.7x10 -22 ). These 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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