Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study.

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) were obtained as instrumental variables (IVs) for these sleep-related traits. Outcome variables were obtained from a public GWAS study that included 14,361 cases and 43,923 European Ancestry controls. The causal relationship between sleep disturbances and RA risk were evaluated by a two-sample Mendelian randomization (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, weighted median, and weight mode methods. MR-Egger Regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to test for horizontal pleomorphism and outliers. There was no evidence of a link between RA and frequent insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), any insomnia (IVW, OR: 1.09; 95% CI: 0.85-1.42; P = 0.489), sleep duration (IVW, OR: 0.65, 95% CI: 0.38-1.10, P = 0.269), getting up (IVW, OR: 0.56, 95% CI: 0.13-2.46, P = 0.442), morningness (IVW, OR: 2.59; 95% CI: 0.73-9.16; P = 0.142), or snoring (IVW, OR: 0.95; 95% CI: 0.68-1.33; P = 0.757). Short sleep duration (6h) had a causal effect on RA, as supported by IVW and weighted median (OR: 1.47, 95% CI: 1.12-1.94, P = 0.006; OR: 1.43, 95%CI:1.01-2.05, P = 0.047). Sensitivity analysis showed that the results were stable. Our findings imply that short sleep duration is causally linked to an increased risk of RA. Therefore, sleep length should be considered in disease models, and physicians should advise people to avoid short sleep duration practices to lower the risk of RA.

Gao RC ，Sang N ，Jia CZ ，Zhang MY ，Li BH ，Wei M ，Wu GC ... -  《Frontiers in Public Health》

Mendelian randomization of individual sleep traits associated with major depressive disorder.

Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, ORivw: 0.998; 95 % CI: 0.996-0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.179; 95 % CI: 1.108-1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, ORivw: 0.991; 95 % CI: 0.924-1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214-1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.519; 95 % CI: 1.376-1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (ORivw: 1.000; 95 % CI: 0.998-1.002, P = 0.906). Obstructive sleep apnea (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) and morning person (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) have no causal effect on the increased risk of MDD. The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD.

Qiu-Qiang Z ，Wei-Wei Y ，Shan-Shu H ，Yi-Ran L ... -  《-》

Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.

Sang N ，Gao RC ，Zhang MY ，Wu ZZ ，Wu ZG ，Wu GC ... -  《Frontiers in Immunology》

Exploring the causal association of rheumatoid arthritis with atrial fibrillation: a Mendelian randomization study.

It has been proved that rheumatoid arthritis (RA) patients have high incidence of atrial fibrillation (AF). Nevertheless, whether they have causal relevance is uncertain. This study aimed to explore and verify the authenticity of causal relationship between RA and AF using Mendelian randomization (MR). The genome-wide association study (GWAS) summary data from Biobank Japan Project (BBJ) (RA, 4199 cases and 208,254 controls) were regarded as exposure data and the GWAS data from European Bio-informatics Institute database (EBI) (AF, 15,979 cases and 102,776 controls) as outcome data. The causal effect was appraised by the inverse variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. MR-robust adjusted profile score (MR-RAPS) method was delivered to examine the robustness of causal relationship and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) method to control horizontal (directional) pleiotropy. The results indicated that RA increased the risk of AF (IVW, the odds ratio (OR) = 1.060; 95% confidence interval (CI), 1.028 to 1.092; p = 1.411 × 10-4; weighted median, OR = 1.046, 95% CI, 1.002 to 1.093, p = 0.047). The MR analysis also showed this causal effect through all four IVW methods with various statistical algorithms. Both MR-RAPS and MR-PRESSO supported the causality of RA and AF. Also, the MR-PRESSO result indicated the absence of apparent pleiotropy. There is a causal association between RA and AF. RA patients are genetically more vulnerable to AF. This study may contribute to further exploring early clinical prevention and fundamental mechanism of AF in patients with RA. Key Points • We provided some genetic evidence for the causal link between rheumatoid arthritis (RA) and atrial fibrillation (AF) with multiple Mendelian randomization (MR) methods. • RA patients were genetically more vulnerable to AF. • This study partly shed light on latent fundamental mechanisms underlying RA-induced AF and inspired future studies on RA-AF relationship.

Rong JC ，Chen XD ，Jin NK ，Hong J ... -  《-》

Causal associations of air pollution with rheumatoid arthritis: A transethnic Mendelian randomization study.

He A ，Li H ，Ouyang S ，He J ，Gong Z ，Zhou Q ，Wang S ，Zhao X ... -  《PLoS One》