TABLE 2.
Causal relations of sleep duration and cardiovascular diseases in Mendelian randomization studies.
| References | Outcomes | Sample | Exposure | Main results | Summary |
| (20) | CAD MI Stroke | Short sleep duration: n = 13,760 cases/66,110 controls and long sleep duration: n = 5629 cases/66,110 controls from Dashti et al.’s GWAS (43) | Short (≤6 h) and long (≥9 h) sleep durations | Short sleep duration: CAD: IVW OR = 1.24, 95% CI: 1.12–1.37; P = 4.09E-05 MI: IVW OR = 1.21, 95% CI: 1.09–1.34; P = 3.81E-04 AIS: IVW OR = 0.99, 95% CI: 0.82–1.20; P = 0.904 ICH: IVW OR = 0.89, 95% CI: 0.68–1.16; P = 0.399 Long sleep duration: CAD: IVW OR = 0.88, 95% CI: 0.69–1.34; P = 0.340 MI: IVW OR = 0.94, 95% CI: 0.73–1.22; P = 0.640 AIS: IVW OR = 1.30, 95% CI: 0.83–2.03; P = 0.245 ICH: IVW OR = 0.89, 95% CI: 0.46–1.71; P = 0.726 Per hour increase in sleep duration MI: IVW OR = 0.90; 95% CI: 0.74–1.09; P = 0.268 CAD: IVW OR = 0.80; 95% CI: 0.66– 0.97; P = 0.021 | Linear and non-linear MR studies consistently show that genetically predicted short sleep duration has a causal and adverse effect on many CVDs, while genetically predicted long sleep duration has no association with the risk of most CVDs. Complementary analyses provided further evidence to support the results. |
| (21) | MI CAD | Short sleep duration: n = 106,192 cases/305,742 controls and long sleep duration: n = 34,184 cases/305,742 controls from Dashti et al.’s GWAS (43); MI: n = 43,676 cases/128,199 controls and CAD: n = 60,801 cases/123,504 controls from Nikpay et al.’s GWAS (84) | Short (<6 h) and long (> 9 h) sleep duration | Short sleep duration: MI: IVW OR = 1.19; 95% CI: 1.09–1.29; P = 4.2e-04 CAD: IVW OR = 1.24; 95% CI: 1.11–1.38; P = 1.79e-06 Per additional hour of sleep MI: IVW OR = 0.80; 95% CI: 0.67–0.95; P = 0.013 CAD: IVW OR = 0.79; 95% CI: 0.68–0.92; P = 3.20e-03 | Two-sample MR studies found a dose-dependent causal association between short sleep duration and MI and CAD. Due to the limited NUMBER of SNPS associated with long sleep duration, no analysis was conducted. The results remained consistent after adjusting for confounding factors. |
| (32) | CHD | Short sleep duration: n = 106,192 cases/305,742 controls and long sleep duration: n = 34,184 cases/305,742 controls from Dashti et al.’s (43) GWAS; CHD: n = 60,801 cases/123,504 controls from Zhu et al.’s GWAS (85) | Sleep duration short (<7 h) and long (≥9 h) sleep duration | Sleep duration: OR = 0.755; 95% CI: 0.658–0.867 Short sleep duration: OR = 4.251; 95% CI: 2.396–7.541 Long sleep duration: OR = 0.208; 95% CI: 0.048–0.897 | MR studies have confirmed that there is a causal association between sleep duration and CHD, short sleep duration increased the risk of CHD, but long sleep duration found no significant causal association. |
| (23) | CAD MI Stroke | Sleep durations: n = 47,180 from Gottlieb et al.’s GWAS (86); CAD: n = 60,801 cases/123,504 controls and MI: n = 43,676 cases/128,197 controls from Nikpay et al.’s GWAS (84); stroke: n = 37,792 cases/397,209 controls from SiGN’ s GWAS (87) | Sleep durations | CAD: IVW OR per 1–SD higher in sleep duration = 1.00; 95% CI: 0.99–1.00; P = 0.162 MI: IVW OR per 1–SD higher in sleep duration = 1.00; 95% CI: 1.00–1.00; P = 0.688 Stroke: IVW OR per 1–SD higher in sleep duration = 1.00; 95% CI: 1.00–1.01; P = 0.231 | There was no evidence of a causal association between sleep duration and CHD, MI, or stroke |
| (22) | CHD | Sleep durations: n = 335,410 from Neale Lab CHD: n = 15,420 cases/15,062 controls from Peden et al.’s GWAS [Coronary Artery Disease (C4D) Genetics Consortium, (88)] | Sleep durations | MR-Egger OR = 9.758; 95% CI: 0.160–592.894; P = 0.286 IVW OR = 0.451; 95% CI: 0.252–0.806; P = 0.007 | The two-sample MR study did not find a causal association between sleep duration and CHD. |
| (36) | HF | Short sleep duration: n = 106,192 cases/305,742 controls and long sleep duration: n = 34,184 cases/305,742 controls from Dashti et al.’s GWAS (43). HF: n = 47,309 cases/930,014 controls from Shah et al.’s GWAS (44). | Short (<7 h) and long (≥9 h) sleep duration | Short sleep duration: IVW OR = 1.136; 95%; CI = 1.025–1.258; P = 0.015 Long sleep duration: IVW OR = 0.921; 95% CI = 0.813–1.045; P = 0.202 | Two-sample MR study showed that genetically predicted short sleep duration increased the risk of HF, but there is no evidence of a causal association between long sleep duration and HF. |
| (35) | HF | Sleep durations: n = 446,118 from Dashti et al.’s GWAS (43). HF: n = 47,309 cases/930,014 controls from Shah et al.’s GWAS (44). | Short (<7 h) and long (≥9 h) sleep duration | Short sleep duration: IVW OR = 1.14; 99% CI: 0.97–1.33; P = 0.041 Long sleep duration: IVW OR = 0.85; 99% CI: 0.65–1.13; P = 0.149 | MR study found that short sleep duration is a causal risk factor of HF, and longer sleep duration may reduce the risk of HF. |
| (43) | HF | N = 30,251 from Karlson et al.’s GWAS (89). | Short (<7 h) and long (≥9 h) sleep duration | Longer sleep duration with congestive heart failure: IVW OR per minute of sleep = 0.978; 95% CI: 0.961–0.996; P = 0.019 | Evidence suggested a causal association between genetically predicted longer sleep duration and reduced risk of HF, sensitivity analyses have a consistent effect. |
| (40) | Stroke | Short sleep duration: n = 106, 192 cases/305,742 controls and long sleep duration: n = 34,184 cases/305,742 controls from Dashti et al.’s GWAS (43); stroke: n = 40,585 cases/406,111 controls from Malik et al.’s GWAS (90) and n = 1,681 cases/2,261 controls from Daniel Woo et al.’s GWAS (91). | Short (<7 h) and long (≥9 h) sleep duration | Short sleep duration: All stroke: IVW OR = 1.13; 95% CI: 1.00–1.27; P = 0.052 AIS: IVW OR = 1.10; 95% CI: 0.97–1.26; P = 0.142 LAS: IVW OR = 1.41; 95% CI: 1.02–1.95; P = 0.040 CES: IVW OR = 0.99; 95% CI: 0.74–1.32; P = 0.938 SVS: IVW OR = 1.02; 95% CI: 0.75–1.37; P = 0.911 Long sleep duration: All stroke: IVW OR = 0.91; 95% CI: 0.78–1.07; P = 0.252 AIS: IVW OR = 0.97; 95% CI: 0.82–1.15; P = 0.723 LAS: IVW OR = 1.25; 95% CI: 0.82–1.91; P = 0.291 CES: IVW OR = 1.35; 95% CI: 0.97–1.88; P = 0.073 SVS: IVW OR = 1.05; 95% CI: 0.71–1.56; P = 0.786 | This study found no causal association between short or long sleep duration and total stroke. Short sleep duration was associated with an increased risk of total ischemic stroke, but sensitivity analyses were less accurate. |
| (39) | Stroke | Short sleep duration: n = 106,192 and long sleep duration: n = 34,184 from Dashti et al.’s GWAS (43); stroke: n = 40,585 cases/406,111 controls from Malik et al.’s GWAS (90) | Short (<7 h) and long (≥9 h) sleep duration | Short sleep duration: All stroke: IVW OR = 0.91; 95% CI: 0.78–1.07; P = 0.25 AIS: IVW OR = 0.96; 95% CI: 0.82–1.12; P = 0.58 LAS: IVW OR = 1.26; 95% CI: 0.85–1.86; P = 0.26 CES: IVW OR = 1.33; 95% CI: 0.98–1.81; P = 0.07 SVS: IVW OR = 0.86; 95% CI: 0.56–1.34; P = 0.51 ICH: IVW OR = 0.55; 95% CI: 0.23–1.29; P = 0.17 Long sleep duration: All stroke: IVW OR = 1.13; 95% CI: 1.00–1.27; P = 0.05 AIS: IVW OR = 1.10; 95% CI: 0.97–1.26; P = 0.14 LAS: IVW OR = 1.41; 95% CI: 1.02–1.95; P = 0.04 CES: IVW OR = 0.99; 95% CI: 0.74–1.32; P = 0.94 SVS: IVW OR = 1.02; 95% CI: 0.75–1.37; P = 0.91 ICH: IVW OR = 1.20; 95% CI: 0.44–3.26; P = 0.72 | Two-sample MR study found no causal association between long and short sleep duration with stroke and related subtypes. |
| (37) | Ischemic stroke and its subtypes | Short sleep duration: n = 106, 192 cases/305,742 controls and long sleep duration: n = 34,184 cases/305,742 controls from Dashti et al.’s GWAS (43); stroke: n = 34,217 cases/406,111 controls from Malik et al.’s GWAS (90) | Short (≤6 h) and long (≥9 h) sleep durations | Per doubling of genetic liability for short sleep duration: LAS: IVW OR = 1.27; 95% CI: 1.01–1.58; P = 0.038 SVS: IVW OR = 1.01; 95% CI: 0.82–1.25 CES: IVW OR = 0.99; 95% CI: 0.83–1.18 AIS: IVW OR = 1.07; 95% CI: 0.98–1.17 Long sleep duration: LAS: IVW OR = 1.17; 95% CI: 0.87–1.56; P = 0.291 SVS: IVW OR = 1.04; 95% CI: 0.79–1.36; P = 0.789 CES: IVW OR = 1.23; 95% CI: 0.98–1.55; P = 0.073 AIS: IVW OR = 0.98; 95% CI: 0.87–1.10; P = 0.723 | Two-sample MR study provided suggestive evidence for a potential causal effect of short sleep duration on the risk of LAS, but not SVS, CES, or AIS. These results were overall robust to sensitivity analyses. |
CAD, coronary artery disease; CHD, coronary heart disease; MI, myocardial infarction; MR, Mendelian randomization; GWAS, genome-wide association study; IVW, inverse-variance weighted; OR, odds ratio; CI, confidence interval; GRS, genetic risk score; SNP, single-nucleotide polymorphism; HF, heart failure; AIS, any ischemic stroke; LAS, large artery stroke; SVS, small vessel stroke; CES, cardioembolic stroke; ICH, primary intracranial hemorrhage.