Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease
Background Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2‐sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. Methods a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.030726 |
| _version_ | 1797296297355509760 |
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| author | Yuwei Li Bin Liu Ying Chen Ziying Liu Ding Ye Yingying Mao Xiaohui Sun |
| author_facet | Yuwei Li Bin Liu Ying Chen Ziying Liu Ding Ye Yingying Mao Xiaohui Sun |
| author_sort | Yuwei Li |
| collection | DOAJ |
| description | Background Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2‐sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. Methods and Results The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome‐wide association study of 8293 European participants. Summary‐level data on CAD were derived from a large genome‐wide association study (71 602 cases and 260 875 controls). We used the inverse‐variance‐weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR‐Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni‐adjusted level of significance (P<1.79×10−3). The odds ratio was 1.20 (95% CI, 1.08–1.33; P=6.83×10−4) per 1‐SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor‐β and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91–0.98]; P=0.007). Conclusions Our findings suggested a risk‐increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation. |
| first_indexed | 2024-03-07T22:02:37Z |
| format | Article |
| id | doaj.art-c96138c4accf4911bd21b1382940800e |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-07T22:02:37Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c96138c4accf4911bd21b1382940800e2024-02-24T04:04:20ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-01-0113210.1161/JAHA.123.030726Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery DiseaseYuwei Li0Bin Liu1Ying Chen2Ziying Liu3Ding Ye4Yingying Mao5Xiaohui Sun6Department of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaDepartment of Epidemiology, School of Public Health Zhejiang Chinese Medical University Hangzhou ChinaBackground Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2‐sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. Methods and Results The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome‐wide association study of 8293 European participants. Summary‐level data on CAD were derived from a large genome‐wide association study (71 602 cases and 260 875 controls). We used the inverse‐variance‐weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR‐Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni‐adjusted level of significance (P<1.79×10−3). The odds ratio was 1.20 (95% CI, 1.08–1.33; P=6.83×10−4) per 1‐SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor‐β and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91–0.98]; P=0.007). Conclusions Our findings suggested a risk‐increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation.https://www.ahajournals.org/doi/10.1161/JAHA.123.030726coronary artery diseasecytokineinflammationMendelian randomization analysis |
| spellingShingle | Yuwei Li Bin Liu Ying Chen Ziying Liu Ding Ye Yingying Mao Xiaohui Sun Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease coronary artery disease cytokine inflammation Mendelian randomization analysis |
| title | Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease |
| title_full | Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease |
| title_fullStr | Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease |
| title_full_unstemmed | Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease |
| title_short | Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease |
| title_sort | genetic evidence for the causal association of circulating cytokines and growth factors with coronary artery disease |
| topic | coronary artery disease cytokine inflammation Mendelian randomization analysis |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.030726 |
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