{
  "abstract": "Background The interplay between genetic susceptibility and clinical risk for incident atrial fibrillation (AF) is unclear.Methods We used a case-cohort study design and included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. The simplified version of the Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF) risk score was used to quantify individual participant clinical risk of incident AF as low (0–3 points), high (4–6 points) and very high risk (7–14 points). We calculated individual participant Genetic Risk Scores (GRS) from 142 variants to categorise participants as low (quintile 1), intermediate (quintile 2–4) or high (quintile 5) genetic risk of AF. We used weighted Cox proportional hazards regression to quantify risk of incident AF according to FIND-AF risk and GRS and assessed the relative excess risk due to interaction (RERI) for interaction on an additive scale.Results During a median follow-up of 12.9 years, 3094 participants developed AF. Compared with individuals with low FIND-AF risk score and low GRS, the multivariable-adjusted HR for AF was 3.47 (95% CI 2.64 to 4.55) for those with high FIND-AF risk score and high GRS and 12.76 (95% CI 5.07 to 32.11) for those with very high FIND-AF risk score and high GRS. The RERI was 0.56 (95% CI 0.43 to 0.70), indicating a positive additive interaction between GRS and FIND-AF risk score.Conclusions Genetic susceptibility and clinical risk interacted on an additive scale to elevate AF risk. These results highlight the need for future research on prevention and screening among individuals with both high genetic and clinical risk for AF.",
  "authors": [
    {
      "affiliations": [
        "Department of Cardiology, Regional Hospital Horsens, Horsens, Central Denmark Region, Denmark",
        "Department of Clinical Medicine, Aarhus University, Aarhus, Central Denmark Region, Denmark"
      ],
      "name": "Tanja Charlotte Frederiksen"
    },
    {
      "affiliations": [
        "Leeds Institute for Data Analytics, University of Leeds, Leeds, UK",
        "Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Ramesh Nadarajah"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, Aarhus University, Aarhus, Central Denmark Region, Denmark",
        "Department of Cardiology, Viborg Regional Hospital, Viborg, Central Denmark Region, Denmark"
      ],
      "name": "Morten Krogh Christiansen"
    },
    {
      "affiliations": [
        "Queen Mary University of London Barts and The London School of Medicine and Dentistry, London, UK"
      ],
      "name": "Jianhua Wu"
    },
    {
      "affiliations": [
        "Division of Epidemiology and Biostatistics, University of Leeds, Leeds, UK"
      ],
      "name": "Chris P Gale"
    },
    {
      "affiliations": [
        "Epidemiology Department, Boston University School of Public Health, Framingham, Massachusetts, USA"
      ],
      "name": "Emelia J Benjamin"
    },
    {
      "affiliations": [
        "Department of Public Health, Aarhus University, Aarhus, Denmark",
        "Danish Cancer Society Research Center, Copenhagen, Capital Region of Denmark, Denmark"
      ],
      "name": "Anja Olsen"
    },
    {
      "affiliations": [
        "Medical Sciences, University of Copenhagen, Kobenhavn, Denmark",
        "Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Faculty of Health Sciences, Copenhagen, Capital Region of Denmark, Denmark"
      ],
      "name": "Mette K Andersen"
    },
    {
      "affiliations": [
        "Medical Sciences, University of Copenhagen, Kobenhavn, Denmark",
        "Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Faculty of Health Sciences, Copenhagen, Capital Region of Denmark, Denmark"
      ],
      "name": "Torben Hansen"
    },
    {
      "affiliations": [
        "Medical Sciences, University of Copenhagen, Kobenhavn, Denmark",
        "Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Faculty of Health Sciences, Copenhagen, Capital Region of Denmark, Denmark"
      ],
      "name": "Niels Grarup"
    },
    {
      "affiliations": [
        "Department of Public Health, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Christina C Dahm"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, Aarhus University, Aarhus, Central Denmark Region, Denmark",
        "Department of Cardiology, Aarhus Universitetshospital, Aarhus N, Denmark"
      ],
      "name": "Henrik Kjærulf Jensen"
    }
  ],
  "title": "Interaction between clinical and genetic risk of atrial fibrillation in the danish diet, cancer and health cohort",
  "uid": "298f837b-6618-5c2b-9dc5-fad721c146d6"
}