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. 2022 Aug 23:13:971997.
doi: 10.3389/fendo.2022.971997. eCollection 2022.

Causal relationships of obesity on musculoskeletal chronic pain: A two-sample Mendelian randomization study

Xiaoqing Chen  1 , Haifeng Tang  1 , Jinding Lin  1 , Rongdong Zeng  1
Affiliations

Causal relationships of obesity on musculoskeletal chronic pain: A two-sample Mendelian randomization study

Xiaoqing Chen et al. Front Endocrinol (Lausanne). .

Abstract

Background: The association between obesity and musculoskeletal chronic pain has attracted much attention these days; however, the causal relationship between them is uncertain. Hence, this study performed a Mendelian randomization (MR) analysis to investigate the causal effects of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on knee pain, hip pain, and back pain.

Materials and methods: The summary data for obesity and musculoskeletal chronic pain came from the genome-wide association study datasets. Significant and independent (p < 5 × 10-8; r2 < 0.001, kb = 10,000) single-nucleotide polymorphisms were extracted for MR analysis. The inverse variance weighted (IVW) and other methods were used for MR analysis, while sensitivity analyses were conducted to test the reliability and stability.

Results: The positive causal effects of BMI on knee pain (odds ratio (OR) = 1.049; 95% CI: 1.034 to 1.063; p = 9.88 × 10-12), hip pain (OR = 1.034; 95% CI: 1.024 to 1.044; p = 1.38 × 10-12), and back pain (OR = 1.022; 95% CI: 1.007 to 1.038; p = 0.004) were observed. WC and HC were also positively associated with knee pain (WC: OR = 1.057; 95% CI: 1.041 to 1.072; p = 1.54 × 10-13; HC: OR = 1.034; 95% CI: 1.017 to 1.052; p = 1.32 × 10-4) and hip pain (WC: OR = 1.031; 95% CI: 1.020 to 1.042; p = 2.61 × 10-8; HC: OR = 1.027; 95% CI: 1.018 to 1.035; p = 5.48 × 10-10) but not back pain. No causal relationship was found between WHR and musculoskeletal chronic pain. The results were robust according to sensitivity tests.

Conclusions: This study revealed that BMI was positively related to knee, hip, and back pain and that WC and HC were positively associated with knee and hip pain, while WHR was not related to any type of musculoskeletal chronic pain.

Keywords: Mendelian randomization; body mass index; chronic pain; hip circumference; waist circumference; waist-to-hip ratio.

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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 Mendelian randomization study. Three assumptions are required. Firstly, the genetic variants should be closely related to the exposures. Secondly, the genetic variants are supposed to be independent of confounding factors. Thirdly, the effects of the genetic variants on outcomes are only mediated by the exposures. SNPs, single-nucleotide polymorphisms.
Figure 2
Figure 2
The Mendelian randomization analysis for causal effects of obesity on knee pain. (A) Forest plot about the causal effect of body mass index on knee pain. (B) Forest plot about the causal effect of waist circumference on knee pain. (C) Forest plot about the causal effect of hip circumference on knee pain. (D) Forest plot about the causal effect of waist-to-hip ratio on knee pain.
Figure 3
Figure 3
The Mendelian randomization analysis for causal effects of obesity on hip pain. (A) Forest plot about the causal effect of body mass index on hip pain. (B) Forest plot about the causal effect of waist circumference on hip pain. (C) Forest plot about the causal effect of hip circumference on hip pain. (D) Forest plot about the causal effect of waist-to-hip ratio on hip pain.
Figure 4
Figure 4
The Mendelian randomization analysis for causal effects of body mass index on back pain. (A) Scatter plot about the causal effect of body mass index on back pain. (B) Forest plot for the overall causal effects of body mass index on back pain. (C) Leave-one-out analysis for the causal effect of body mass index on back pain. (D) Funnel plot of SNPs related to body mass index and back pain. SNPs, single-nucleotide polymorphisms.
See this image and copyright information in PMC

References

    1. González-Muniesa P, Mártinez-González M-A, Hu FB, Després J-P, Matsuzawa Y, Loos RJF, et al. . Obesity. Nat Rev Dis Primers (2017) 3:17034. doi: 10.1038/nrdp.2017.34 - DOI - PubMed
    1. Morris A. Subtyping obesity. Nat Rev Endocrinol (2019) 15(6):316. doi: 10.1038/s41574-019-0201-y - DOI - PubMed
    1. Litwin M, Kułaga Z. Obesity, metabolic syndrome, and primary hypertension. Pediatr Nephrol (2021) 36(4):825–37. doi: 10.1007/s00467-020-04579-3 - DOI - PMC - PubMed
    1. Al-Sulaiti H, Diboun I, Agha MV, Mohamed FFS, Atkin S, Dömling AS, et al. . Metabolic signature of obesity-associated insulin resistance and type 2 diabetes. J Transl Med (2019) 17(1):348. doi: 10.1186/s12967-019-2096-8 - DOI - PMC - PubMed
    1. Liu Y, Ding W, Wang HL, Dai LL, Zong WH, Wang YZ, et al. . Gut microbiota and obesity-associated osteoarthritis. Osteoarthritis Cartilage (2019) 27(9):1257–65. doi: 10.1016/j.joca.2019.05.009 - DOI - PubMed

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