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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

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

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.

KEYWORDS:

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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