Table 1. Association of the HCN4 variant with outcomes in the UK Biobank using prospective and cause-specific hazard competing risk analyses.
| Outcome | Model | N total | N events | HR (95% CI) * | P-value |
|---|---|---|---|---|---|
| Genetic model for SHIFT** | |||||
| Using participants without a history of atrial fibrillation or heart failure at recruitment | |||||
| Heart failure | Cox proportional-hazards | 404,767 | 3,385 | 0.96 (0.89, 1.02) | 0.18 |
| Atrial fibrillation | Cox proportional-hazards | 404,767 | 8,461 | 1.08 (1.04, 1.13) | 9.4 × 10−5 |
| Heart failure | Competing risk (atrial fibrillation) | 404,767 | 2,380 | 0.90 (0.83, 0.98) | 0.013 |
| Atrial fibrillation | Competing risk (heart failure) | 404,767 | 7,663 | 1.08 (1.04, 1.13) | 3.2 × 10−4 |
| Genetic model for SIGNIFY** | |||||
| Using participants without a history of atrial fibrillation or MI at recruitment | |||||
| MI or CV Death | Cox proportional-hazards | 397,008 | 4,976 | 0.99 (0.94, 1.05) | 0.84 |
| Atrial fibrillation | Cox proportional-hazards | 397,008 | 7,880 | 1.08 (1.04, 1.13) | 3.1 × 10−4 |
| MI or CV Death | Competing risk (atrial fibrillation) | 397,008 | 4,534 | 0.99 (0.93, 1.04) | 0.61 |
| Atrial fibrillation | Competing risk (MI or CV death) | 397,008 | 7,482 | 1.09 (1.04, 1.13) | 1.4 × 10−4 |
* Reporting the effect of the heart rate reducing allele of rs8038766 at the HCN4 gene. All models were adjusted for age, sex and the first 10 principal components. In the Cox proportional-hazards models, individuals were censored at the time of death or end of follow up; in the competing risk models, individuals were censored at the time of occurrence of the competing event, death, or end of follow up.
** Our model aims to match the outcome and exposure of interest from the SHIFT and SIGNIFY trials, but we did not emulate the trials in any other way such as by matching the inclusion / exclusion criteria.
CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction.