Several studies have indicated the involvement of increased free thyroxine (FT4) and decreased thyrotropin in the increased risk of atrial fibrillation (AF). However, direct involvement is yet to be established. This study aims to investigate whether thyroid traits are directly associated with the risk of AF.

This mendelian randomization (MR) study included a total of 11 studies with 7,679 individuals and 49,233 referents. The researchers used genome-wide significant variants as instruments for measuring standardized FT4 and thyrotropin levels within the reference range, FT3: FT4 ratio, hyperthyroidism, hypothyroidism, and standardized thyroid peroxidase antibody levels. The primary outcome of the study was prevalent and incident AF.

In multivariable analysis, the pooled hazard ratio of FT4 levels for incident AF was 1.55, and the odds ratio for prevalent AF was 2.80. The FT4 genetic risk was linearly associated with FT4 by 0.082 standard error. However, the findings suggested that gene-based increased FT3: FT4 ratio, increased hypothyroidism, and increased thyrotropin within the reference range were associated with the increased risk of AF. Lastly, AF also showed positive associations with gene-based hyperthyroidism.

The research concluded that gene-based hyperthyroidism and increased FT3: FT4 ratio was associated with an increased risk of AF, whereas hypothyroidism and increased thyrotropin was reduced the risk of AF.