| Title: | A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity |
| Journal: | npj Genomic Medicine |
| Published: | 20 Sep 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31552141/ |
| DOI: | https://doi.org/10.1038/s41525-019-0097-4 |
| URL: | https://www.nature.com/articles/s41525-019-0097-4.pdf |
Publication 7640
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Abstract
Growing evidence suggests that inflammation is a significant contributor to different cardiovascular diseases (CVDs). Mendelian randomization (MR) was performed to assess the causal inference between plasma soluble IL6 receptor (sIL6R), a negative regulator of IL6 signaling, and different cardiovascular and immune-related disorders. Cis-MR with multiple instrumental variables showed an inverse association of sIL6R with rheumatoid arthritis, atrial fibrillation, stroke, coronary artery disease, and abdominal aortic aneurysm. However, genetically-determined sIL6R level was positively associated with atopic dermatitis and asthma. Also, sIL6R level was associated with longevity, as evaluated by parental age at death, a heritable trait. Gene-based association analysis with S-PrediXcan by using tissues from GTExV7 showed that IL6R tissue expression-disease pair associations were consistent with the directional effect of IL6 signaling identified in MR. Genetically-determined reduced IL6 signaling lowers the risk of multiple CVDs and is associated with increased longevity, but at the expense of higher atopic risk.8 Authors
- Mickael Rosa
- Arnaud Chignon
- Zhonglin Li
- Marie-Chloé Boulanger
- Benoit J. Arsenault
- Yohan Bossé
- Sébastien Thériault
- Patrick Mathieu
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