# Causal Association of Circulating Adipokines With the Risk of Carpal Tunnel Syndrome and Diabetic Neuropathy: A Bidirectional Two‐Sample Mendelian Randomization Study

## TL;DR

This study found no strong evidence that certain fat-related proteins cause carpal tunnel syndrome or diabetic neuropathy.

## Contribution

The study used genetic data to investigate causal links between adipokines and two neuropathies for the first time.

## Key findings

- No significant causal associations were found between adiponectin, leptin, resistin, or IL-6 and carpal tunnel syndrome.
- No significant causal associations were found between these adipokines and diabetic neuropathy.
- Results suggest that confounders like obesity and hyperglycemia may influence the observed relationships.

## Abstract

This study is aimed at exploring the causal association between genetically predicted serum levels of circulating adipokines and the risk of carpal tunnel syndrome (CTS) and diabetic neuropathy (DN). A two‐sample bidirectional Mendelian randomization (MR) design was employed, using the inverse‐variance weighted (IVW), weighted median, weighted mode, and MR‐Egger regression methods. Sensitivity tests included MR‐Egger, MR‐PRESSO, Cochran′s Q, and leave‐one‐out methods. A total of 52 single‐nucleotide polymorphisms (SNPs) associated with adiponectin, leptin, resistin, and IL‐6 levels were selected as instrumental variables (IVs). With adiponectin as exposure, no statistically significant causal association was confirmed for CTS (OR [95% CI]: 1.0331 [0.8257–1.2925], p = 0.776) or DN (OR [95% CI]: 0.865 [0.5385–1.3894], p = 0.549). With leptin levels as exposure, no statistically significant causal association was confirmed for CTS (OR [95% CI]: 0.8958 [0.5069–1.583], p = 0.705) or DN (OR [95% CI]: 1.6745 [0.6704–4.1828], p = 0.270) as well. With IL‐6 levels as exposure, no statistically significant causal association for CTS (OR [95% CI]: 1.0037 [0.9627–1.0465], p = 0.861) or DN (OR [95% CI]: 1.0213 [0.9177–1.1366], p = 0.699) was found. With resistin levels as exposure, no statistically significant causal association was confirmed for CTS (OR [95% CI]: 0.9867 [0.8452–1.1518], p = 0.865) or DN (OR [95% CI]: 0.9751 [0.7358–1.2924], p = 0.861). The result of MR‐Egger regression and other sensitivity methods suggested that analyses are robust and not affected by horizontal pleiotropy. This study did not find the conclusive evidence that genetically predicted levels of adiponectin, leptin, resistin, and IL‐6 are causally associated with the risk of CTS or DN. The relationship between circulating adipokines and neuropathies is most likely heavily moderated by confounders, such as obesity and hyperglycemia.