Table 2.
Summary of findings of MR analyses performed to determine causality between various sleep traits (exposures) and disease outcomes
| Disease outcome | Sleep exposure | MR model | Interpretation | Reference |
|---|---|---|---|---|
| Sleep and neurodegenerative diseases | ||||
| Cognition | Sleep duration | One and two sample MR | Positive association between short sleep duration and cognitive decline | [61] |
| Risk for Alzheimer’s disease | Sleep duration | Two sample MR | No causal association determined | [61] |
| Sleep traits | Two sample MR | No causal association determined | [62] | |
| Sleep disturbances | Bidirectional two-sample MR | AD had a causal effect on sleep disturbances, but sleep disturbances were not causal to AD | [63] | |
| Parkinson’s disease | Sleep traits | Two sample MR | No causal association determined | [64] |
| Neurodegenerative disease risk | Sleep/wake patterns | Two sample MR | Chronotype was inversely associated with Parkinson’s age of onset Sleep efficiency was associated with decreased AD risk Daytime sleepiness was associated with increased ALS risk |
[60] |
| Amyotrophic Lateral Sclerosis (ALS) | Sleep disturbances | Two sample MR | Daytime sleepiness was associated with increased ALS risk | [65] |
| Pain | Sleep disturbances | Bidirectional two-sample MR | Chronic pain had a causal effect on sleep disturbances, but sleep disturbances were not causal for pain | [66] |
| Insomnia | Bidirectional two-sample MR | Causal association between insomnia and pain was determined in both directions | [67] | |
| MR of sleep and psychiatric disorders | ||||
| Depression | Sleep duration | Two sample MR | Sleep duration was associated with decreased risk of depression | [68] |
| Daytime napping | Two sample MR | Daytime napping was associated with increased risk of depression | [68] | |
| Chronotype | Two sample MR | Chronotype was associated with decreased risk of depression | [69] | |
| Insomnia | Bidirectional multivariable MR | Causal association between insomnia and depression was determined in both directions | [70] | |
| Insomnia | Bidirectional MR | Causal association between insomnia and depression was determined in both directions | [71] | |
| Schizophrenia | Insomnia | Bidirectional MR | No causal association determined in either direction | [72] |
| Chronotype | Two sample MR | No causal association determined | [73] | |
| Sleep duration | Bidirectional two-sample MR | Long sleep duration is associated with pathogenesis of schizophrenia | [39] | |
| Bipolar disorder | Insomnia | Bidirectional MR | Insomnia had a causal effect on bipolar disorder, but bipolar disorder was not causal for insomnia | [72] |
| Autism Spectrum Disorder (ASD) | Insomnia | Bidirectional MR | Insomnia had a causal effect on ASD, but ASD was not causal for insomnia | [72] |
| MR of sleep and cardiometabolic disease | ||||
| Adiposity | Insomnia | Two sample MR | Insomnia had a causal effect on increased measure of adiposity | [74] |
| increased waist circumference | Daytime napping | Two sample MR | Daytime napping had a causal association with increased waist circumference | [74] |
| BMI (adult) | Sleep duration | Two sample MR | Long sleep duration had a causal association with increased adult BMI | [75] |
| Sleep duration | Two sample MR | Long sleep duration had a causal association with increased adult BMI | [76] | |
| Chronotype | Two sample MR | No causal association determined | [77] | |
| Daytime napping | Two sample MR | No causal association determined | [78] | |
| Snoring | Multivariable MR | Causal association between high BMI and snoring was identified | [24] | |
| BMI(Children) | Sleep duration | Two sample MR | Long sleep duration had a causal association with decreased BMI in children (2–10 years) | [79] |
| Atrial fibrillation | Obstructive sleep apnea (OSA) | Two sample MR | OSA had a causal association with increased risk of atrial fibrillation | [80] |
| Obstructive sleep apnea (OSA) | Bidirectional MR | OSA had a causal effect on atrial fibrillation, but atrial fibrillation was not causal for OSA | [81] | |
| Type 2 Diabetes (T2D) | Insomnia | Univariable/Multivariable MR | Insomnia had a causal association with T2D | [82] |
| Insomnia | Two sample MR | Insomnia had a causal association with T2D | [83] | |
| Sleep duration | Two sample MR | No causal association determined | [84] | |
| Chronotype | Two sample MR | No causal association determined | [77] | |
| Myocardial infarction (MI) | Sleep duration | Two sample MR | Short sleep duration was causally associated with MI | [85] |
| Heart failure | Sleep duration | Two sample MR | Longer sleep duration was causally associated with decreased risk for heart failure. | [86] |
| Cardiovascular diseases (CVDs) | Sleep duration | Two sample MR | Short sleep duration was causally associated with increased risk of CVDs | [87] |
| Insomnia | Two sample MR | Insomnia was causally associated with nine CVD traits | [88] | |
| Insomnia | Two sample MR | Insomnia was causally associated with overall CVD risk | [89] | |
| Stroke | Insomnia | Two sample MR | Insomnia was causally associated with increased risk for Stroke | [90] |
| Sleep duration | Two sample MR | No causal association determined | [91] | |
| Hypertension | Insomnia | Two sample MR | Insomnia was causally associated with increased risk for hypertension | [92] |
| Sleep duration | Two sample MR | Longer sleep duration was causally associated with decreased risk for hypertension | [92] | |
| MR of sleep and cancer | ||||
| Breast cancer | Chronotype | One and two sample MR | Chronotype was causally associated with decreased risk for breast cancer | [93] |
| Obstructive sleep apnea (OSA) | Two sample MR | OSA was causally associated with increased risk for breast cancer | [94] | |
| Prostate cancer | Chronotype | Univariable/Multivariable MR | Chronotype was causally associated with decreased risk for prostate cancer | [95] |
| Lung cancer | Insomnia | Two sample/Multivariable MR | Insomnia was causally associated with increased risk for lung cancer | [96] |
| Insomnia | Two sample MR | Insomnia was causally associated with increased risk for lung cancer | [97] | |
| Insomnia | Two sample MR | Insomnia was causally associated with increased risk for lung cancer | [98] | |
| MR of sleep and other health outcomes | ||||
| Peptic ulcer | Insomnia | Bidirectional MR | Insomnia was causally associated with increased risk for peptic ulcer | [99] |
| Osteoarthritis | Insomnia | Univariable/Multivariable MR | Insomnia was causally associated with increased risk for osteoarthritis | [100] |
| Sleep duration | Univariable/Multivariable MR | Short sleep duration was causally associated with increased risk for osteoarthritis | [100] | |
| Chronic kidney disease | Sleep duration | Two sample MR | Long sleep duration was causally associated with increased risk for chronic kidney disease* | [101] |
*Identified only in individuals with diabetes.