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NPJ Genom Med. 2019 Sep 20;4:23. doi: 10.1038/s41525-019-0097-4. eCollection 2019.

A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity.

Author information

1Laboratory of Cardiovascular Pathobiology, Quebec Heart and Lung Institute/Research Center, Department of Surgery, Laval University, Quebec, Canada.
2Department of Medicine, Laval University, Quebec, Canada.
3Department of Molecular Medicine, Laval University, Quebec, Canada.
4Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec, Canada.
Contributed equally


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.


Cardiovascular diseases; Genetics research

Conflict of interest statement

Competing interestsP.M. is a consultant for Casebia Therapeutics. The rest of the authors declare no competing interests.

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