Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Abstract Background Sleep traits are associated with cardiometabolic disease risk, evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery risk. We combined adjusted multivariable regression (AMV) MR analyses of phenotypes unfavourable on 113 metabolomic to investigate possible biochemical mechanisms linking cardiovascular disease. Methods used AMV ( N = 17,368) two-sample 38,618) examine effects self-reported symptoms, total habitual duration, chronotype traits. The were conducted data 10 cohorts mostly Europeans, for age, sex, body mass index. For the analyses, we summary results published European-ancestry genome-wide association studies nuclear magnetic resonance (NMR) serum metabolites. inverse-variance weighted (IVW) method complemented this sensitivity assess assumptions. Results found consistent associations usual vs. sometimes/rare/never lower citrate (? 0.08 standard deviation (SD)[95% confidence interval (CI) ? 0.12, 0.03] in 0.03SD [? 0.07, 0.003] MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] 0.06SD [0.03, 0.10) MR]), very large HDL particles 0.04SD 0.08, 0.00] 0.05SD 0.09, 0.02] phospholipids 0.002] MR). Longer creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.15SD [0.02, 0.29] MR) isoleucine (0.22SD [0.08, 0.35]). No was observed measures. Conclusions Whilst our suggested may not cause widespread metabolic disruption, some notable observed. longer might explain effects, these heart disease, which warrant further investigation.