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Body composition and atrial fibrillation: a Mendelian randomization study.

Emmi Tikkanen1,2, Stefan Gustafsson3, Joshua W Knowles1,2,4

  • 1Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA, USA.

European Heart Journal
|February 6, 2019
PubMed
Summary

Increases in both fat-free mass and fat mass independently increase the risk of atrial fibrillation (AF). This genetic link highlights distinct causal pathways contributing to AF development.

Keywords:
Atrial fibrillationBioimpedanceCausal effectFat massFat-free massGenetics

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Area of Science:

  • Cardiovascular Genetics
  • Metabolic Health
  • Epidemiology

Background:

  • Observational studies link increased fat-free mass and fat mass to higher atrial fibrillation (AF) risk.
  • The independent causal roles of these body composition measures in AF remain unclear.

Purpose of the Study:

  • To investigate the independent causal effects of fat-free mass and fat mass on the risk of incident atrial fibrillation.
  • Utilize Mendelian randomization to assess causality beyond observational associations.

Main Methods:

  • Employed a large UK Biobank cohort (N=487,404) with incident AF events (N=10,365).
  • Utilized two-sample Mendelian randomization with genetic instruments for fat-free mass and fat mass.
  • Applied multivariate Mendelian randomization to evaluate independent causal effects.

Main Results:

  • Both fat-free mass and fat mass showed observational associations with increased AF risk.
  • Mendelian randomization revealed causal effects: fat-free mass (IVW HR=1.55) and fat mass (IVW HR=1.30).
  • Multivariate MR confirmed independent causal contributions of fat-free mass (RR=1.37) and fat mass (RR=1.28) to AF risk.

Conclusions:

  • Genetically determined increases in fat-free mass independently contribute to atrial fibrillation risk.
  • Genetically determined increases in fat mass also independently contribute to atrial fibrillation risk.
  • These findings elucidate distinct causal pathways linking body composition to AF.