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Background: While observational data suggest a higher risk of coronary artery disease with frequent egg consumption, only limited and inconsistent data are available on the relation of egg consumption with stroke. Objective: To test the hypothesis that egg consumption is positively associated with the incidence of ischemic stroke among Veterans. Methods: The Million Veteran Program is an ongoing observational study designed to study genetic determinants of chronic diseases among Veterans (2011 to now). Egg consumption was self-reported at baseline using validated Willett food questionnaires. We used ICD 9 codes 433, 434, 436, 437.0, and 437.6 and ICD 10 codes I63, I65, I66, I67.2, I67.6 and I67.8 to identify ischemic stroke using previously validated algorithm and multivariable Cox proportional hazard model to estimate relative risks. Results: A total of 234,032 Veterans provided data on egg consumption and were free of stroke at baseline. Mean age at baseline was 65.6 (SD: 11.7) years and 91.6% (214,373 of 234,032) were men. Median egg consumption was 2-4 eggs per week. During a mean follow up of 3.2 years, a total of 5,747 new cases of fatal or non-fatal acute ischemic stroke occurred. Crude incidence rates for acute ischemic stroke were 6.5, 7.2, 7.1, 7.4, 8.0, and 8.3 cases per 1000 person-years for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, and ≥ 1/day, respectively. Corresponding adjusted hazard ratios (95% CI) were 1.00 (ref), 1.10 (0.97-1.25), 1.10 (0.97-1.25), 1.13 (1.00 -1.27), 1.19 (1.04-1.37), and 1.25 (1.09-1.44) controlling for age, sex, ethnicity, body mass index, education, smoking, alcohol intake, and overall diet quality (p linear trend 0.0007). The egg-stroke relation was not modified by body mass index, sex, or diabetes status. Conclusion: Egg consumption is positively associated with incidence of acute ischemic stroke among Veterans.

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Introduction: Observational studies have implicated atrial fibrillation (AF) as a risk factor for a number of cardiovascular diseases (CVD). Whether AF is causally related to these CVD is unknown. Methods: We included participants with both electronic health record-derived phenotypes and imputed genotype data in this study. A genetic instrument for AF consisting of 406 common variants was derived using a pruning and thresholding method (r2<0.3; p-value <5x10-8) on the 2018 AF Genetics Consortium GWAS summary statistics. 1- and 2-sample MR analyses were performed. In 2-sample MR, the inverse-variance weighted method was used as the primary analysis. Additional sensitivity analyses were performed to account for potential violations of the instrumental variable assumptions. Results: We included 615,635 participants in the study (440,690 European, 118,531 African, 48,908 Hispanic, 7,506 Asian ancestry). Genetic risk of AF was associated with heart failure in both 1-sample (OR/log odds of genetically predicted AF =1.18, 95% CI 1.15 - 1.20) and 2-sample MR (OR/log odds of genetically predicted AF =1.13, 95% CI 1.11 - 1.15). Additionally, genetic risk of AF was associated with heart failure subtypes and non-ischemic cardiomyopathy. There was no association between genetic risk of AF and pulmonary embolism (PE) or deep venous thrombosis (DVT), however, genetic risk of AF was associated with PE after excluding individuals with concurrent or prior DVT (OR1-sample MR 1.08, 95% CI 1.01 - 1.15; OR2-sample MR 1.06, 95% CI 1.03 - 1.08). Lastly, we confirmed an association between genetic risk of AF and ischemic stroke but not all-cause dementia. Our results were robust to a number of sensitivity analyses. Conclusions: In a large multi-ancestry study, we delineate the potential causal contribution of AF to a number of CVD and highlight support for a causal association between AF and isolated PE. Our findings inform how prevention and treatment of AF may affect CVD incidence and outcomes.