Mendelian Randomization Study on Causal Association of Il-6 With Intelligence

Abstract

Jinming Qiu, Bin Zhai, Min Zhang, Qi Zeng, Gaizhi Zhu, Ran Gao, He Xiao, Wenting Su and Renxi Wang

Objective Previous observational studies have shown the association of IL-6 levels and intelligence. The present two-sample MR study aims to identify the genetic causal link between IL-6 and intelligence.

Methods IL-6 signaling and its negative regulator soluble IL-6 receptor (sIL-6R) genetic instrumental variants were chosen from IL-6-signaling-associated genome-wide association studies (GWAS) (204,402 European individuals) and sIL-6R-associated GWAS (1650 European individuals), respectively. Intelligence GWAS (149,051 European participants) were used to evaluate the causal link between IL-6 and intelligence by performing a two-sample MR study.

Results We found that as IL-6-signaling genetically increased, intelligence significantly decreased using IVW (odds ratio [OR] = 0.828, 95% confidence interval [CI]: 0.702–0.975, p = 0.024) and weighted mode (OR = 0.865, 95% CI: 0.749–0.999, p = 0.049). Conversely, as genetic changes of sIL-6R increased, intelligence significantly increased using Wald ratio (OR = 1.052, 95% CI: 1.000–1.107, p = 0.049).

Conclusions Our analysis suggests that genetically increased IL-6-signaling reduces intelligence, whereas genetically increased sIL-6R upregulates intelligence. Thus, IL-6 may be a risk factor for intelligence.

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