Mendelian randomization study on occupational cold exposure and frozen shoulder

doi:10.3877/cma.j.issn.1674-134X.2025.05.001

Abstract

Abstract:

Objective

To evaluate the causal association between occupational severe cold exposure and the risk of frozen shoulder using Mendelian randomization (MR), and to provide evidence for occupational health interventions.

Methods

A two-sample MR design was conducted using exposure data from the UK Biobank and outcome data from the FinnGen database. Genetic variants significantly associated with severe cold exposure were employed as instrumental variables. The inverse variance-weighted method was the primary approach for causal effect estimation, supplemented by sensitivity analyses to ensure robustness.

Results

The results indicated a significant association between occasional severe cold exposure and an increased risk of frozen shoulder [odds ratio (OR) = 2.78, 95% confidence interval (CI) (1.17, 6.57), P=0.020]. No significant associations were observed for rare or frequent severe cold exposure. Sensitivity analyses confirmed the robustness of these findings.

Conclusion

MR study indicates causal evidence linking severe cold exposure to frozen shoulder risk, occasional exposure to severe cold environments may represent a key risk factor for frozen shoulder.

Key words: Occupational exposure, Bursitis, Mendelian randomization analysis, Causality

Liu Chen, Guojun Liang, Yushu Chen, Xintao Liu. Mendelian randomization study on occupational cold exposure and frozen shoulder[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(05): 521-527.

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URL: https://zhgjwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-134X.2025.05.001

https://zhgjwkzz.cma-cmc.com.cn/EN/Y2025/V19/I05/521

Figures/Tables 5

Figure 1 The results of the MR (Mendelian randomization) analysis of exposure and outcomeNote: SNP-single nucleotide polymorphism; OR-odds ratio; CI-confidence interval; OR>1indicates that the exposure is a risk factor for the outcome; OR<1 indicates that the exposure is a protective factor for the outcome; if the upper and lower bounds of OR (95% CI) are both greater than one or less than one, and P<0.05, the difference is statistically significant

Figure 2 Scatter plot of MR (Mendelian randomization) analysis of exposure and outcome

Figure 3 Sensitivity analysis results. A to C are the funnel plots for the MR (Mendelian randomization) analysis of whether exposure to extreme cold environment and frozen shoulder; A represents rarely exposure; B represents sometimes exposure; Figure C represents often exposure; D to F are the forest plots for the "leave-one-out" method analysis of whether exposure to extreme cold environment; D represents rarely exposure; E represents sometimes exposure; F represents often exposureNote: The symmetry of the funnel plot indicates the absence of significant heterogeneity; the "leave-one-out" analysis shows that the results with significant causal relationships remain stable after each single nucleotide polymorphism is excluded one by one

Table 1 Sensitivity analysis on sever cold work environment and frozen shoulder

结局Outcome	暴露Exposure	分析方法Methods	Q	Q_df	Q_pval	Egger截距Egger intercept	SE	P值	MR-PRESSO全局性测试Global test of MR-PRESSO
冻结肩Frozen shoulder	很少/从不会Rarely or never	MR Egger	6.660	9	0.672	0.029	0.017	0.134	0.505
	很少/从不会Rarely or never	IVW	9.376	10	0.497
	有时会Sometimes	MR Egger	4.449	7	0.727	-0.002	0.027	0.949	0.835
	有时会Sometimes	IVW	4.453	8	0.814
	经常Often	MR Egger	10.727	16	0.826	-0.005	0.014	0.709	0.877
	经常Often	IVW	10.872	17	0.863

Table 2 Co-location analysis on sever cold work environment and frozen shoulder

暴露序列Trait-exposure	结果序列Trait-outcome	SNP	PPH0	PPH1	PPH2	PPH3	PPH4
很少或从不会暴露Rarely or never	冻结肩frozen shoulder	412	0.0244	0.8813	0.0014	0.0514	0.0415
有时会暴露Sometimes		503	0.0026	0.9688	0.0000	0.0166	0.0119
经常会暴露Often		361	0.0247	0.9239	0.0004	0.0163	0.0347

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