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. 2021 Jul 22:12:688849.
doi: 10.3389/fgene.2021.688849. eCollection 2021.

Obesity, Type 2 Diabetes, and the Risk of Carpal Tunnel Syndrome: A Two-Sample Mendelian Randomization Study

Jiarui Mi  1 , Zhengye Liu  2
Affiliations

Obesity, Type 2 Diabetes, and the Risk of Carpal Tunnel Syndrome: A Two-Sample Mendelian Randomization Study

Jiarui Mi et al. Front Genet. .

Abstract

Some previous observational studies have reported an increased risk of carpal tunnel syndrome (CTS) in patients with obesity or type 2 diabetes (T2D), which was however, not observed in some other studies. In this study we performed a two-sample Mendelian randomization to assess the causal effect of obesity, T2D on the risk of CTS. Single nucleotide polymorphisms associated with the body mass index (BMI) and T2D were extracted from genome-wide association studies. Summary-level results of CTS were available through FinnGen repository. Univariable Mendelian randomization (MR) with inverse-variance-weighted method indicated a positive correlation of BMI with CTS risk [odds ratio (OR) 1.66, 95% confidence interval (CI), 1.39-1.97]. Genetically proxied T2D also significantly increased the risk of CTS [OR 1.17, 95% CI (1.07-1.29)]. The causal effect of BMI and T2D on CTS remained consistent after adjusting for each other with multivariable MR. Our mediation analysis indicated that 34.4% of BMI's effect of CTS was mediated by T2D. We also assessed the effects of several BMI and glycemic related traits on CTS. Waist circumference and arm fat-free mass were also causally associated with CTS. However, the associations disappeared after adjusting for the effect of BMI. Our findings indicate that obesity and T2D are independent risk factors of CTS.

Keywords: Mendelian randomization; body mass index; carpal tunnel syndrome; obesity; type 2 diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The diagram of the study design and three assumptions of Mendelian randomization. The obesity-related exposures include arm fat mass, arm fat-free mass, and waist circumference. Lipid components include HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides. SNP, single nucleotide polymorphism; BMI, body mass index; T2D, type 2 diabetes.
FIGURE 2
FIGURE 2
Univariable MR and multivariable MR analyses showed genetically proxied BMI and T2D were independent risk factors of carpal tunnel syndrome. Univariable MR was performed with IVW, weighted median, and MR-PRESSO methods. Multivariable MR was performed to assess the effect of T2D on CTS adjusted for BMI and the effect of BMI adjusted for T2D. *No outlier detected. IVW, inverse-variance-weighted; BMI, body mass index; T2D, type 2 diabetes; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization.
FIGURE 3
FIGURE 3
Univariable MR and multivariable MR analyses showing the associations of genetically proxied obesity-related factors with carpal tunnel syndrome. 1 SD increase of arm fat mass, arm fat-free mass, and waist circumference showed increased risk of carpal tunnel syndrome with outliers adjusted by MR-PRESSO. However, the causal associations were absent after adjustment for BMI. *No outlier detected. IVW, inverse-variance-weighted; BMI, body mass index; SD, standard deviation; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization.
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