Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study
The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelia...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.667097/full |
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| author | Kun Xiang Kun Xiang Peng Wang Zhiwei Xu Yu-Qian Hu Yu-Qian Hu Yi-Sheng He Yi-Sheng He Yue Chen Yue Chen Ya-Ting Feng Ya-Ting Feng Kang-Jia Yin Kang-Jia Yin Ji-Xiang Huang Ji-Xiang Huang Jie Wang Jie Wang Zheng-Dong Wu Zheng-Dong Wu Xiao-Ke Yang De-Guang Wang Dong-Qing Ye Dong-Qing Ye Hai-Feng Pan Hai-Feng Pan |
| author_facet | Kun Xiang Kun Xiang Peng Wang Zhiwei Xu Yu-Qian Hu Yu-Qian Hu Yi-Sheng He Yi-Sheng He Yue Chen Yue Chen Ya-Ting Feng Ya-Ting Feng Kang-Jia Yin Kang-Jia Yin Ji-Xiang Huang Ji-Xiang Huang Jie Wang Jie Wang Zheng-Dong Wu Zheng-Dong Wu Xiao-Ke Yang De-Guang Wang Dong-Qing Ye Dong-Qing Ye Hai-Feng Pan Hai-Feng Pan |
| author_sort | Kun Xiang |
| collection | DOAJ |
| description | The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk. |
| first_indexed | 2024-12-17T22:19:52Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T22:19:52Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-0b97f264f57d47e18d57f6489945b5cc2022-12-21T21:30:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.667097667097Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization StudyKun Xiang0Kun Xiang1Peng Wang2Zhiwei Xu3Yu-Qian Hu4Yu-Qian Hu5Yi-Sheng He6Yi-Sheng He7Yue Chen8Yue Chen9Ya-Ting Feng10Ya-Ting Feng11Kang-Jia Yin12Kang-Jia Yin13Ji-Xiang Huang14Ji-Xiang Huang15Jie Wang16Jie Wang17Zheng-Dong Wu18Zheng-Dong Wu19Xiao-Ke Yang20De-Guang Wang21Dong-Qing Ye22Dong-Qing Ye23Hai-Feng Pan24Hai-Feng Pan25Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaCenter for Genetic Epidemiology and Genomics, School of Public Health, Soochow University Medical College, Suzhou, ChinaSchool of Public Health, Faculty of Medicine, University of Queensland, Brisbane, QLD, AustraliaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Nephrology, Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, ChinaInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, ChinaThe observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.https://www.frontiersin.org/articles/10.3389/fimmu.2021.667097/fullautoimmune diseaseMendelian randomizationgut microbiomesystemic lupus erythematosuscausality |
| spellingShingle | Kun Xiang Kun Xiang Peng Wang Zhiwei Xu Yu-Qian Hu Yu-Qian Hu Yi-Sheng He Yi-Sheng He Yue Chen Yue Chen Ya-Ting Feng Ya-Ting Feng Kang-Jia Yin Kang-Jia Yin Ji-Xiang Huang Ji-Xiang Huang Jie Wang Jie Wang Zheng-Dong Wu Zheng-Dong Wu Xiao-Ke Yang De-Guang Wang Dong-Qing Ye Dong-Qing Ye Hai-Feng Pan Hai-Feng Pan Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study Frontiers in Immunology autoimmune disease Mendelian randomization gut microbiome systemic lupus erythematosus causality |
| title | Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study |
| title_full | Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study |
| title_fullStr | Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed | Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study |
| title_short | Causal Effects of Gut Microbiome on Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study |
| title_sort | causal effects of gut microbiome on systemic lupus erythematosus a two sample mendelian randomization study |
| topic | autoimmune disease Mendelian randomization gut microbiome systemic lupus erythematosus causality |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.667097/full |
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