Insight into the relationship between resting heart rate and atrial fibrillation: a Mendelian randomization study

Figures

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  Figure 1. An illustration of the Mendelian randomization approach. The genetic instrument is used as a proxy to estimate the causal effect of the exposure on the outcome. The Mendelian randomization approach is based on three assumptions (i) the genetic instrument is associated with the exposure, (ii) the genetic instrument is not associated with any confounders, and (iii) the genetic instrument influences the outcome only through the exposure. RHR, resting heart rate; AF, atrial fibrillation.

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  Figure 2. An illustration of the concept of Mendelian randomization and a randomized controlled trial, and how they are comparable to each other. Both methods are used to assess causality, and a randomized controlled trial is considered the gold standard for assessing causality.

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  Figure 3. The observed relationship between resting heart rate and risk of atrial fibrillation plotted with the estimated restricted cubic spline using five knots in UK Biobank to the left and the Trøndelag health study to the right. Resting heart rate in beats per minute is on the x-axis and the log odds of atrial fibrillation is on the y-axis. The solid line is the dose-response curve between resting heart rate and risk of atrial fibrillation, and the dotted line represents the 95% confidence interval.

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  Figure 4. The causal association between resting heart rate and risk of atrial fibrillation from non-linear Mendelian randomization. Here, the resting heart rate distribution is divided into 100 strata, and an estimate from linear Mendelian randomization is made in each stratum. The black line is the dose-response curve between resting heart rate and risk of atrial fibrillation, with the grey lines indicating the 95% confidence intervals, in UK Biobank to the left and The Trøndelag Health Study to the right. AF, atrial fibrillation.