Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study
BackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut micro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.971376/full |
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| author | Yuxuan Zhang Xinyi Zhang Delong Chen Jia Lu Qinyan Gong Jiacheng Fang Jun Jiang Jun Jiang |
| author_facet | Yuxuan Zhang Xinyi Zhang Delong Chen Jia Lu Qinyan Gong Jiacheng Fang Jun Jiang Jun Jiang |
| author_sort | Yuxuan Zhang |
| collection | DOAJ |
| description | BackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10−8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10−5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.ResultsBased on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 – 1.10, P = 1.67 × 10−4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75–0.93, P = 7.76 × 10−4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74–0.92, P = 4.15 × 10−4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.ConclusionOur findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome. |
| first_indexed | 2024-04-14T01:54:38Z |
| format | Article |
| id | doaj.art-a77c6bf0fc0d4f138b2f47795740ab31 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-14T01:54:38Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-a77c6bf0fc0d4f138b2f47795740ab312022-12-22T02:19:09ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.971376971376Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization studyYuxuan Zhang0Xinyi Zhang1Delong Chen2Jia Lu3Qinyan Gong4Jiacheng Fang5Jun Jiang6Jun Jiang7Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, The First People's Hospital of Jiashan, Jiaxing, ChinaDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaCardiovascular Key Laboratory of Zhejiang Province, Hangzhou, ChinaBackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10−8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10−5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.ResultsBased on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 – 1.10, P = 1.67 × 10−4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75–0.93, P = 7.76 × 10−4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74–0.92, P = 4.15 × 10−4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.ConclusionOur findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.https://www.frontiersin.org/articles/10.3389/fcvm.2022.971376/fullMendelian randomizationgut microbiomecardiovascular diseasecausalityOxalobacterClostridiaceae |
| spellingShingle | Yuxuan Zhang Xinyi Zhang Delong Chen Jia Lu Qinyan Gong Jiacheng Fang Jun Jiang Jun Jiang Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study Frontiers in Cardiovascular Medicine Mendelian randomization gut microbiome cardiovascular disease causality Oxalobacter Clostridiaceae |
| title | Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study |
| title_full | Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study |
| title_fullStr | Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study |
| title_full_unstemmed | Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study |
| title_short | Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study |
| title_sort | causal associations between gut microbiome and cardiovascular disease a mendelian randomization study |
| topic | Mendelian randomization gut microbiome cardiovascular disease causality Oxalobacter Clostridiaceae |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.971376/full |
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