Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study

Xiang, Kun; Wang, Peng; Xu, Zhiwei; Hu, Yun; He, Yisheng; Chen, Yue; Feng, Ya-Ting; Yin, Kang-Jia; Huang, Jianguo; Wang, Jie; Wu, Zhengdong; Yang, Xiao‐Ke; Wang, Deguang; Ye, Dong-Qing; Pan, Hai‐Feng

doi:10.3389/fimmu.2021.667097

Cited by 136 publications

(134 citation statements)

References 40 publications

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“…( 14 ) and Xiang et al. ( 15 ) performed MR analyses to investigate the effects of gut microbiota on IBD and SLE, respectively. Our study differs from their studies in the following three aspects: First, our study is more comprehensive in its investigation of ADs.…”

Section: Discussionmentioning

confidence: 99%

“…The above two studies fall short in that they treat gut microbiota composition as a whole without distinguishing specific taxa, while different microbial taxa may have distinct effects on human health. During the preparation of this article, Zhang et al (14) and Xiang et al (15) investigated the causal effects of specific microbial taxa on two ADs, inflammatory bowel disease (IBD) and SLE. However, studies on other ADs are still sparse.…”

Section: Introductionmentioning

confidence: 99%

“…( 14 ) and Xiang et al. ( 15 ) investigated the causal effects of specific microbial taxa on two ADs, inflammatory bowel disease (IBD) and SLE. However, studies on other ADs are still sparse.…”

Section: Introductionmentioning

confidence: 99%

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Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

et al. 2022

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BackgroundGrowing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.ObjectiveTo reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.Materials and MethodsWe assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.ResultsCombining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339–1.922; PFDR = 4.19 × 10−7] and CeD (OR: 1.401; 95% CI, 1.139–1.722; PFDR = 2.03 × 10−3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus.ConclusionThis study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

et al. 2022

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“…R 2 denotes the exposure variance of the chosen SNPs interpretation, n is the sample size, and K represents the number of instrumental variables included. If F is <10, there is a weak relationship between the IVs and exposure ( 26 ); that they are unrelated to confounding factors (independence assumption); and that they influence the outcome solely through their effects on the exposure of interest (exclusion restriction assumption), implying that there is no horizontal pleiotropic effect between IV and outcomes ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

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

Gao

Sang

Jia

et al. 2022

Front. Public Health

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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.

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“…Sleep duration can also affect the functional correlation of intestinal microbiota and its metabolic integrity (10). In addition, a recent Mendelian randomization (MR) analysis showed that intestinal microbial components had a causal impact on the risk of SLE (11). Therefore, sleep may have an impact on SLE pathogenesis through gut microbes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study

Cited by 136 publications

References 40 publications

Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

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

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

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