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Research Article

Stable methylation loci are associated with systolic blood pressure in a Croatian island population

    Alexander C Sprague

    Division of Epidemiology, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    ,
    Liang Niu

    Division of Biostatistics & Bioinformatics, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    ,
    Roman Jandarov

    Division of Biostatistics & Bioinformatics, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    ,
    Xiang Zhang

    Division of Environmental Genetics & Molecular Toxicology, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    ,
    Ge Zhang

    Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA

    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    ,
    Aimin Chen

    Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

    ,
    Jelena Šarac

    Institute for Anthropological Research, Zagreb, Croatia

    ,
    Miran Čoklo

    Institute for Anthropological Research, Zagreb, Croatia

    ,
    Sasa Missoni

    Institute for Anthropological Research, Zagreb, Croatia

    ,
    Pavao Rudan

    Anthropological Center & Scientific Council for Anthropological Research, Croatian Academy of Arts & Sciences, Zagreb, Croatia

    ,
    Scott M Langevin

    *Author for correspondence: Tel.: +1 513 558 1066;

    E-mail Address: langevst@uc.edu

    Division of Epidemiology, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA

    &
    Ranjan Deka

    Division of Epidemiology, Department of Environmental & Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA

    Published Online:https://doi.org/10.2217/epi-2022-0279

    Background: The objective was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among an adult population from the Croatian island of Hvar. Materials & methods: An epigenome-wide association study was conducted using peripheral blood longitudinally collected at two time points 10 years apart via Infinium MethylationEPIC beadarray (n = 112). Stable and dynamic loci were identified using linear mixed models. Associations between cardiometabolic traits and loci were assessed using linear models. Results: 22 CpG loci were significantly associated with systolic blood pressure. Twenty were stable and two were dynamic. Conclusion: Multiple genes may be involved in the determination of systolic blood pressure level via stable epigenetic programming, potentially established earlier in life.

    Plain language summary

    Cardiovascular disease is the leading cause of death worldwide. Previous studies have found that genetics incompletely explain susceptibility to cardiovascular disease. To find new potential risk factors, the authors investigated the possible contribution of DNA methylation (modifications to DNA that can affect gene expression but do not alter the underlying genetic code) in an adult population on the Croatian island of Hvar, which has a high number of people with cardiovascular and metabolic disease. By examining DNA methylation in blood collected at two time points, 10 years apart, the authors were able to identify DNA methylation that either stayed the same over time (stable) or changed the most over time (dynamic). These were then compared with clinical test results related to cardiovascular or metabolic diseases to determine if they are associated. Twenty-two methylation sites were found to be associated with systolic blood pressure. Of those, 20 were considered stable and two were dynamic. Additionally, there was one stable methylation site associated with serum calcium and one with C-reactive protein. These findings suggest that systolic blood pressure may be regulated through stable DNA methylation that is potentially established earlier in life.

    Tweetable abstract

    New research from @UC_CoMResearch describes an epigenome-wide association study that suggests an association between stable methylation at multiple loci and adult systolic blood pressure levels.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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