Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions

JACC Basic to Translational Science 2026 Open access

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Authors: Azin Kheirkhah, Silvia Di Maio, Stefan Coassin, Sebastian Schönherr, Claudia Lamina, Lukas Forer, Florian Kronenberg, Johanna F. Schachtl‐Riess
DOI: 10.1016/j.jacbts.2026.101564
Cited by: 1
References: 75

Abstract

In the study at hand, 2-sample Mendelian randomization supported a causal effect of interleukin-6 receptor (IL-6R) signaling on Lp(a) concentrations, revealing a direct interplay between 2 causal risk factors for cardiovascular disease (CVD). Importantly, epidemiological analyses in UK Biobank showed that neglecting the IL-6R functional state can confound the association between IL-6 levels and Lp(a). However, the effect of circulating IL-6 on Lp(a) concentrations was modest even when the functional state of the receptor was considered. In line, factorial Mendelian randomization indicated that down-regulation of IL-6R signaling and Lp(a) independently reduce CVD risk, highlighting complementary opportunities for CVD risk mitigation.

Fields of Study & Subjects

Lipoproteins and Cardiovascular Health Adipokines Inflammation and Metabolic Diseases Atherosclerosis and Cardiovascular Diseases

Publication details

Journal / source
JACC Basic to Translational Science
Publisher
Elsevier BV
Volume
11
Issue
8
Pages
101564–101564
Publication date
8 May 2026
Language
EN