Causal association of lifestyle factors, clinical features in the risk of sleep disorders: Based on mendelian randomization analysis
Authors: Xu Jingyu , Wang Baojuan , Zhu Wenbin , Ao Haiqing 
Published: December 2024

Objective: To identify potential genetic risk factors for sleep disorders (SD) and to explore the causal associations between lifestyle factors and clinical features with SD, given the limitations of traditional observational studies.
Methods: Data from published genome-wide association studies (GWAS) were analyzed, encompassing 34 lifestyle factors and 17 clinical features as potential exposures influencing SD. These analyses yielded information on 51 exposures and 4 outcomes. Outcomes consisted of four categories: non-organic sleep disorders (NSD), narcolepsy, rapid eye movement (REM) sleep behavior disorders (RSBD), and obstructive sleep apnea (OSA). All genetic variables for exposure and outcome were derived from individuals of European ancestry. Two-sample MR analysis was conducted, with inverse variance weighted (IVW) as the primary method for evaluating causal effects. Weighted median estimation (WME), MR-Egger (MRE), simple mode (SM), and weighted mode (WM) were used as supplementary evaluation methods.
Results:
(1) The protective factors causally associated with NSD include overall physical activity time (OR: 0.35; 95%CI: 0.13-0.99; P=0.048) and fresh fruit intake (OR: 0.30; 95%CI: 0.12-0.75; P=0.010).
(2) The risk factors that are causally related to narcolepsy include smoking (OR: 1.02; 95%CI: 1.01-1.03; P=0.001), alcoholic drinks (OR: 1.02; 95%CI: 1.01-1.03; P=0.013 and OR: 1.02; 95%CI: 1.01-1.03; P<0.001), cereal intake (OR: 1.03; 95%CI: 1.00-1.07; P=0.029), salad/raw vegetable intake (OR: 1.10; 95%CI: 1.03-1.16; P=0.002), TDI (OR: 1.05; 95%CI: 1.00-1.10; P=0.036), overall health rating (OR: 1.07; 95%CI: 1.05-1.10; P<0.001), BMI (OR: 1.02; 95%CI: 1.02-1.03; P<0.001), FINS (OR: 1.06; 95%CI: 1.03-1.09; P<0.001), TG (OR: 1.02; 95%CI: 1.01-1.03; P<0.001) and hypertension (OR: 1.08; 95%CI: 1.02-1.15; P=0.011).
(3) The protective factors causally associated with narcolepsy include tea intake (OR: 0.95; 95%CI: 0.93-0.97; P<0.001), non-oily fish intake (OR: 0.91; 95%CI: 0.84-0.99; P=0.021), years of schooling (OR: 0.97; 95%CI: 0.96-0.99; P<0.001), cognitive performance (OR: 0.98; 95%CI: 0.97-0.99; P=0.001), average total household income before tax (OR: 0.94; 95%CI: 0.93-0.96; P<0.001), ApoA-I (OR: 0.99; 95%CI: 0.99-1.00; P=0.036), HDL (OR: 0.99; 95%CI: 0.98-0.99; P<0.001).
(4) The risk factors that are causally related to OSA include smoking (OR: 1.20; 95%CI: 1.08-1.34; P=0.001 and OR: 1.15; 95%CI: 1.06-1.25; P=0.001), alcohol intake (OR: 1.12; 95%CI: 1.01-1.24; P=0.037), coffee intake (OR: 1.25; 95%CI: 1.00-1.56; P=0.046), pork intake (OR: 2.55; 95%CI: 1.37-4.74; P=0.003), TDI (OR: 1.56; 95%CI: 1.12-2.19; P=0.009), overall health rating (OR: 2.76; 95%CI: 2.20-3.46; P<0.001), BMI (OR: 1.97; 95%CI: 1.85-2.11; P<0.001), WHR (OR: 1.30; 95%CI: 1.08-1.55; P=0.004), TG (OR: 1.06; 95%CI: 1.02-1.11; P=0.009), hypertension (OR: 2.72; 95%CI: 1.73-4.26; P<0.001) and CRP (OR: 1.06; 95%CI: 1.01-1.11; P=0.016).
(5) The protective factors causally associated with OSA include bread intake (OR: 0.63; 95%CI: 0.49-0.83; P=0.001), cereal intake (OR: 0.71; 95%CI: 0.56-0.90; P=0.005), dried fruit intake (OR: 0.64; 95%CI: 0.50-0.83; P=0.001), years of schooling (OR: 0.72; 95%CI: 0.66-0.79; P<0.001), cognitive performance (OR: 0.79; 95%CI: 0.71-0.87; P<0.001), average total household income before tax (OR: 0.78; 95%CI: 0.66-0.93; P=0.005), FPG (OR: 0.84; 95%CI: 0.75-0.94; P=0.003), ApoA-I (OR: 0.94; 95%CI: 0.90-0.99; P=0.017) and HDL (OR: 0.89; 95%CI: 0.85-0.93; P<0.001).
(6) After multivariate analysis through adjusting BMI, the causal association between ApoA-I, TG, HDL and narcolepsy still exists. The causal association between hypertension and OSA still exists.
Conclusions: The evidence from this study suggests that among 34 lifestyle factors: (1) overall physical activity time and fresh fruit intake are protective factors for NSD. (2) Smoking and alcohol drinks, cereal intake, salad/raw vegetable intake, poverty, poor overall health rating, and high BMI are risk factors for narcolepsy. Tea intake, non oily fish intake, education and cognition, and high income are protective factors for narcolepsy. (3) Smoking and alcohol intake, coffee intake, pork intake, poverty, poor overall health rating, high BMI, and high WHR are risk factors for OSA. Bread and cereal intake, dried fruit intake, education and cognition, and high income are protective factors for OSA. Among the 17 clinical features: (1) hypertension is a risk factor for NSD. (2) High FINS, high TG, hypertension, and high CRP are risk factors for narcolepsy. ApoA-I and HDL are protective factors for narcolepsy. (3) High TG, hypertension, and high CRP are risk factors for OSA. FPG, ApoA-I, and HDL are protective factors for OSA. There is not enough evidence to suggest that other relationships meet the criteria for causal association established.