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The link between liver fat and 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)
- Univ Oslo, Norway; Univ Oslo, Norway; Maastricht Univ, Netherlands
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- Gurholt, Tiril P. (author)
- Univ Oslo, Norway; Univ Oslo, Norway
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- Sonderby, Ida E. (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Oslo Univ Hosp, Norway; Univ Oslo, Norway
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- Shadrin, Alexey A. (author)
- Univ Oslo, Norway; Univ Oslo, Norway
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- Hindley, Guy (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Kings Coll London, England
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- Rahman, Zillur (author)
- Univ Oslo, Norway; Univ Oslo, Norway
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- de Lange, Ann-Marie G. (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Lausanne Univ Hosp CHUV, Switzerland; Univ Lausanne, Switzerland; Univ Oxford, England
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- Frei, Oleksandr (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Univ 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 Med, Linkoping, Sweden
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- Linge, Jennifer (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,AMRA Med, Linkoping, Sweden
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- Simon, Rozalyn (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV
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- Beck, Dani (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Univ Oslo, Norway; Diakonhjemmet Hosp, Norway
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- Westlye, Lars T. (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Univ Oslo, Norway; Univ Oslo, Norway
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- Halvorsen, Sigrun (author)
- Oslo Univ Hosp Ulleval, Norway; Univ Oslo, Norway
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- Dale, Anders M. (author)
- Univ Calif San Diego, CA 92037 USA
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- Karlsen, Tom H. (author)
- Univ Oslo, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway
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- Kaufmann, Tobias (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Univ Tubingen, Germany
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- Andreassen, Ole A. (author)
- Univ Oslo, Norway; Univ Oslo, Norway; Univ Oslo, Norway
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(creator_code:org_t)
- 2022-11-19
- 2022
- English.
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In: Communications Biology. - : NATURE PORTFOLIO. - 2399-3642. ; 5:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- A GWAS study of European individuals uncovers genetic associations between whole-body MRI derived measures and cardiometabolic diseases and highlights the key role of liver fat in cardiometabolic health. 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.
Subject headings
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Klinisk vetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Clinical Science (hsv//eng)
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- ref (subject category)
- art (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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Sonderby, 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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Beck, Dani
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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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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Clinical Science
- Articles in the publication
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Communications B ...
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Linköping University