Abstract Aims Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with risk of incident AF, and test the modification effect of genetic susceptibility. Methods and results A total of 305,627 participants with detailed information for time from waking to first cigarette were enrolled from UK Biobank database. Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. Weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13,410 AF cases were documented. Compared to non-smokers, time from waking to the first cigarette showed gradient inverse associations with risk of incident AF (P-trend &amp;lt;0.001). The adjusted hazard ratio related to smoking timing was 1.13 (95% CI: 0.96-1.34) for &amp;gt;120 minutes, 1.20 (95% CI: 1.01-1.42) for 61-120 minutes, 1.34 (95% CI: 1.19-1.51) for 30-60 minutes, 1.43 (95% CI: 1.26-1.63) for 5-15 minutes, and 1.49 (95% CI: 1.24-1.63) for &amp;lt;5 minutes, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF. Conclusions Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF.

Smoking timing, genetic susceptibility, and the risk of incident atrial fibrillation: a large prospective cohort study