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Topics {✒️}

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         headline:Steatotic liver disease interacts with a polygenic risk score for triglyceride clearance to impact the risk of hypertriglyceridaemia: The Maastricht Study
         description:The pathogenesis of hypertriglyceridaemia is explained by a complex interplay between genetic and environmental factors. We hypothesised that intrahepatic lipid (IHL) content, which drives the production of triacylglycerol-rich VLDL particles, interacts with a polygenic risk score (PRS) for triglyceride clearance to impact the risk of hypertriglyceridaemia. We used data from The Maastricht Study, a population-based prospective cohort study (n=3810; age: 60 years, 48% women, 10% hypertriglyceridaemia, 26% steatotic liver disease). We performed multivariable linear regression analyses to assess the impact of the cross-sectional interaction between IHL content (quantified by MRI) and a PRS for triglyceride clearance (based on nine SNPs) on fasting serum triglycerides, after adjustment for sociodemographic, lifestyle and cardiovascular risk factors. We subsequently explored whether a similar longitudinal interaction affects incident CVD during a 10 year follow-up. There was an impact of interaction between IHL content and the PRS for triglyceride clearance on serum triglycerides (p=0.005). The strength of the association between a high PRS and risk of hypertriglyceridaemia was larger in individuals with steatotic liver disease (OR 6.196; 95% CI 3.966, 9.768) than in those without (OR 1.618; 95% CI 1.110, 2.380). A similar trend was observed for incident CVD risk (p=0.078). Genetically predisposed individuals have a substantially higher risk of hypertriglyceridaemia when they also have steatotic liver disease. This gene–environment interaction might contribute to more personalised treatment approaches, which require further exploration in future studies.
         datePublished:2025-06-27T00:00:00Z
         dateModified:2025-06-27T00:00:00Z
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            Interaction
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      headline:Steatotic liver disease interacts with a polygenic risk score for triglyceride clearance to impact the risk of hypertriglyceridaemia: The Maastricht Study
      description:The pathogenesis of hypertriglyceridaemia is explained by a complex interplay between genetic and environmental factors. We hypothesised that intrahepatic lipid (IHL) content, which drives the production of triacylglycerol-rich VLDL particles, interacts with a polygenic risk score (PRS) for triglyceride clearance to impact the risk of hypertriglyceridaemia. We used data from The Maastricht Study, a population-based prospective cohort study (n=3810; age: 60 years, 48% women, 10% hypertriglyceridaemia, 26% steatotic liver disease). We performed multivariable linear regression analyses to assess the impact of the cross-sectional interaction between IHL content (quantified by MRI) and a PRS for triglyceride clearance (based on nine SNPs) on fasting serum triglycerides, after adjustment for sociodemographic, lifestyle and cardiovascular risk factors. We subsequently explored whether a similar longitudinal interaction affects incident CVD during a 10 year follow-up. There was an impact of interaction between IHL content and the PRS for triglyceride clearance on serum triglycerides (p=0.005). The strength of the association between a high PRS and risk of hypertriglyceridaemia was larger in individuals with steatotic liver disease (OR 6.196; 95% CI 3.966, 9.768) than in those without (OR 1.618; 95% CI 1.110, 2.380). A similar trend was observed for incident CVD risk (p=0.078). Genetically predisposed individuals have a substantially higher risk of hypertriglyceridaemia when they also have steatotic liver disease. This gene–environment interaction might contribute to more personalised treatment approaches, which require further exploration in future studies.
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      dateModified:2025-06-27T00:00:00Z
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         Hypertriglyceridaemia
         Interaction
         Polygenic risk score
         Steatotic liver disease
         Internal Medicine
         Metabolic Diseases
         Human Physiology
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            address:
               name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
            name:Maastricht University
            address:
               name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
      name:Tos T. J. M. Berendschot
      affiliation:
            name:University Eye Clinic Maastricht, Maastricht University Medical Center
            address:
               name:University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
      name:Abraham A. Kroon
      affiliation:
            name:Maastricht University Medical Center
            address:
               name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
            name:Maastricht University
            address:
               name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
      name:Alfons J. H. M. Houben
      affiliation:
            name:Maastricht University Medical Center
            address:
               name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
            name:Maastricht University
            address:
               name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
      name:Coen D. A. Stehouwer
      affiliation:
            name:KU Leuven
            address:
               name:Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
               type:PostalAddress
            type:Organization
      name:Martijn C. G. J. Brouwers
      affiliation:
            name:Maastricht University Medical Center
            address:
               name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
            name:Maastricht University
            address:
               name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
            name:Maastricht University
            address:
               name:Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands
      name:Department of Epidemiology, Maastricht University, Maastricht, the Netherlands
      name:Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands
      name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
      name:Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
      name:Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
      name:Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands

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