ArticleBrain and behavior2025
A Mendelian Randomization Study and Experimental Validation Investigating the Potential Relationship Among Interleukin-6 Receptor Subunit Beta, Obesity, and Alzheimer's Disease.
Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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5 authors.
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Abstract
objectiveThis study employs Mendelian randomization (MR) aimed at systematically evaluating the relationship among interleukin-6 receptor subunit beta, obesity, and Alzheimer's disease (AD). We conducted animal studies to validate the reliability of the MR analytical outcomes.
methodsThe pooled data for the interleukin-6 receptor subunit beta originated from the genome-wide association study (GWAS) dataset, which included a total of 10,534,735 participants. Obesity pooled data were from the GWAS dataset (case n = 23,971 and control n = 388,084) and AD pooled data from the GWAS database (case n = 39,106 and control n = 46,828). The aforementioned data sets facilitated MR causal analysis. First, utilize the inverse variance weighting (IVW) method for analysis and enhance it with MR-Egger regression and weighted median approaches, and a sensitivity analysis was performed by MR-multiple effect residuals and outliers (MR-Presso), Cochran Q test, and Leave-one (LOO) analysis. We established an obesity model by feeding 6-week-old male ApoE
resultsMR analysis indicated that a genetically predicted increase in interleukin-6 receptor subunit beta raises the risk of AD (OR = 1.064, 95% CI: 1.021-1.109, p = 0.003). The exposure factor interleukin-6 receptor subunit beta served as a protective element against obesity (OR = 0.9372,95%CI:0.8921-0.9847, p = 0.010). Obesity showed an adverse relationship with AD. As the body mass index (BMI) increased, the risk of developing AD decreased (OR = 0.9299, 95% CI: 0.8939-0.9674, p ＜0.001). ELISA findings revealed that the levels of interleukin-6 receptor subunit beta (gp130), oncostatin-M (OSM), and IL-6 in serum and hippocampus decreased in obesity, whereas they increased in AD, aligning with the results of the MR Analysis.
conclusionIn summary, our extensive Mendelian randomization data suggest that increased levels of the interleukin-6 receptor subunit beta may be associated with a reduced risk of obesity, and consequently, may increase the risk of AD.
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