• Iyas Daghlas, Hassan S Dashti, Jacqueline Lane, Krishna G Aragam, Martin K Rutter, Richa Saxena, and Céline Vetter.
• Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
• J. Am. Coll. Cardiol. 2019 Sep 10; 74 (10): 1304-1314.

BackgroundObservational studies suggest associations between extremes of sleep duration and myocardial infarction (MI), but the causal contribution of sleep to MI and its potential to mitigate genetic predisposition to coronary disease is unclear.ObjectivesThis study sought to investigate associations between sleep duration and incident MI, accounting for joint effects with other sleep traits and genetic risk of coronary artery disease, and to assess causality using Mendelian randomization (MR).MethodsIn 461,347 UK Biobank (UKB) participants free of relevant cardiovascular disease, the authors estimated multivariable adjusted hazard ratios (HR) for MI (5,128 incident cases) across habitual self-reported short (<6 h) and long (>9 h) sleep duration, and examined joint effects with sleep disturbance traits and a coronary artery disease genetic risk score. The authors conducted 2-sample MR for short (24 single nucleotide polymorphisms) and continuous (71 single nucleotide polymorphisms) sleep duration with MI (n = 43,676 cases/128,199 controls), and replicated results in UKB (n = 12,111/325,421).ResultsCompared with sleeping 6 to 9 h/night, short sleepers had a 20% higher multivariable-adjusted risk of incident MI (HR: 1.20; 95% confidence interval [CI]: 1.07 to 1.33), and long sleepers had a 34% higher risk (HR: 1.34; 95% CI: 1.13 to 1.58); associations were independent of other sleep traits. Healthy sleep duration mitigated MI risk even among individuals with high genetic liability (HR: 0.82; 95% CI: 0.68 to 0.998). MR was consistent with a causal effect of short sleep duration on MI in CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus Coronary Artery Disease Genetics Consortium) (HR: 1.19; 95% CI: 1.09 to 1.29) and UKB (HR: 1.21; 95% CI: 1.08 to 1.37).ConclusionsProspective observational and MR analyses support short sleep duration as a potentially causal risk factor for MI. Investigation of sleep extension to prevent MI may be warranted.Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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