Mendelian randomization analysis of causality between blood cells and tonsil and adenoid associated chronic diseases

doi:10.3877/cma.j.issn.1674-0785.2026.01.008

Abstract

Abstract:

Objective

To explore the bidirectional causal relationship between blood cells and chronic diseases of the tonsil and adenoid (CDTA).

Methods

Eighty peripheral blood specimens were collected from patients with CDTA who were treated at the Department of Otorhinolaryngology, Head and Neck Surgery of Huai'an Second People's Hospital between January 2024 and January 2025. Meanwhile, 40 blood samples were collected from healthy controls. The age range of the included samples was 5 to 18 years old. The differences in the quantity of peripheral blood cells were compared. Based on two-sample Mendelian randomization (MR), using the "TwoSampleMR" R package, and comprehensively employing three estimation methods including inverse variance weighted (IVW), MR-Egger regression, and weighted median, bidirectional causal association analysis was conducted on genome-wide association study (GWAS) summary data for 91 blood cell traits and CDTA. Heterogeneity was tested by Cochran's Q statistics. The MR-Egger intercept was used for horizontal pleiotropy test. The influence of single nucleotide polymorphisms (SNPs) on IVW results was evaluated by the leave-one-out analysis, and the potential bias of strongly correlated SNPs was evaluated by funnel plot.

Results

A difference was observed in the count of peripheral blood neutrophils. Forward MR analysis showed that neutrophil perturbation response (wdf Colchicine 20 h NE4 SD SF) (odds ratio [OR]=0.970, 95% confidence interval [CI]: 0.947~0.993, P=0.011), red blood cell perturbation response (ret Rotenone 6h overnight RBC SD FSC) (OR=0.969, 95%CI: 0.940~0.999, P=0.045), and white blood cell perturbation response (pltf Baseline WBC1 Med SSC) (OR=1.026, 95%CI: 1.003~1.050, P=0.025) had a causal association with the occurrence of CDTA. Reverse MR analysis showed that CDTA had a causal association with monocyte perturbation response (wdf TMAO 3.5 h MO2 Med SSC) (OR=2.048, 95%CI: 1.044~4.020, P=0.037), neutrophil perturbation response (wdf Pam3CSK4 19 h NE4 CV FSC) (OR=1.402, 95%CI: 1.034~1.902, P=0.030), red blood cell perturbation response (ret DMSO 4.5 h RBC1 SD FSC) (OR=0.261, 95%CI: 0.083~0.819, P=0.021), and reticulocyte perturbation response (ret Ciprofloxacin 22 h RET1 Med SSC) (OR=0.713, 95%CI: 0.538~0.943, P=0.018). Sensitivity analysis showed no heterogeneity or pleiotropy.

Conclusion

There is a bidirectional causal relationship between blood cells and CDTA. The results of this study provide a basis for clinical prevention, diagnosis, and treatment of CDTA.

Key words: Blood cells, Tonsils, Adenoids, Mendelian randomization

Huazhong Cheng, Shucheng Wu, Susu Yue, Li Guan, Jun Dai, Fang Yuan, Yuan Zong, Shuo Li, De Huai, Haixu Wang. Mendelian randomization analysis of causality between blood cells and tonsil and adenoid associated chronic diseases[J]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(01): 49-57.

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Figures/Tables 9

References 20

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暴露	结局	方法	nSNP	Beta	OR（95% CI）	P值
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	MR Egger	6	-0.038	0.962（0.868~1.067）	0.508
		Weighted median	6	-0.026	0.975（0.945~1.005）	0.104
		Inverse variance weighted	6	-0.031	0.970（0.947~0.993）	0.011^*
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	MR Egger	6	-0.035	0.965（0.710~1.313）	0.833
		Weighted median	6	-0.024	0.976（0.942~1.012）	0.189
		Inverse variance weighted	6	-0.031	0.969（0.940~0.999）	0.044^*
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	MR Egger	18	0.044	1.045（0.957~1.142）	0.343
		Weighted median	18	0.027	1.028（0.999~1.057）	0.057
		Inverse variance weighted	18	0.026	1.026（1.003~1.050）	0.025^*

暴露	结局	方法	nSNP	Beta	OR（95% CI）	P值
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	MR Egger	6	-0.038	0.962（0.868~1.067）	0.508
		Weighted median	6	-0.026	0.975（0.945~1.005）	0.104
		Inverse variance weighted	6	-0.031	0.970（0.947~0.993）	0.011^*
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	MR Egger	6	-0.035	0.965（0.710~1.313）	0.833
		Weighted median	6	-0.024	0.976（0.942~1.012）	0.189
		Inverse variance weighted	6	-0.031	0.969（0.940~0.999）	0.044^*
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	MR Egger	18	0.044	1.045（0.957~1.142）	0.343
		Weighted median	18	0.027	1.028（0.999~1.057）	0.057
		Inverse variance weighted	18	0.026	1.026（1.003~1.050）	0.025^*

暴露	结局	Cochran'sQ分析			MR-Egger回归
暴露	结局	方法	Cochran's Q	P值	Egger_intercept	SE	P值
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	MR Egger	4.788	0.310	0.002	0.015	0.891
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	Inverse variance weighted	4.813	0.439	0.002	0.015	0.891
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	MR Egger	7.677	0.104	0.001	0.039	0.981
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	Inverse variance weighted	7.679	0.175	0.001	0.039	0.981
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	MR Egger	25.113	0.068	-0.004	0.010	0.683
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	Inverse variance weighted	25.385	0.086	-0.004	0.010	0.683

暴露	结局	Cochran'sQ分析			MR-Egger回归
暴露	结局	方法	Cochran's Q	P值	Egger_intercept	SE	P值
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	MR Egger	4.788	0.310	0.002	0.015	0.891
中性粒细胞细胞扰动反应（wdf Colchicine 20 h NE4 SD SF）	扁桃体和腺样体慢性疾病	Inverse variance weighted	4.813	0.439	0.002	0.015	0.891
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	MR Egger	7.677	0.104	0.001	0.039	0.981
红细胞扰动反应（ret Rotenone 6 h overnight RBC SD FSC）	扁桃体和腺样体慢性疾病	Inverse variance weighted	7.679	0.175	0.001	0.039	0.981
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	MR Egger	25.113	0.068	-0.004	0.010	0.683
白细胞扰动反应（pltf Baseline WBC1 Med SSC）	扁桃体和腺样体慢性疾病	Inverse variance weighted	25.385	0.086	-0.004	0.010	0.683

暴露	结局	方法	nSNP	Beta	OR（95% CI）	P值
扁桃体和腺样体慢性疾病	单核细胞扰动反应（wdf TMAO 3.5 h MO2 Med SSC）	MR Egger	31	1.665	5.283 (0.320~87.255)	0.254
		Weighted median	31	1.026	2.791 (1.077~7.231)	0.035^*
		Inverse variance weighted	31	0.717	2.048 (1.044~4.020)	0.037^*
扁桃体和腺样体慢性疾病	中性粒细胞扰动反应（wdf Pam3CSK4 19 h NE4 CV FSC）	MR Egger	31	0.480	1.616 (0.442~5.902)	0.474
		Weighted median	31	0.395	1.484 (0.985~2.236)	0.059
		Inverse variance weighted	31	0.338	1.402 (1.034~1.902)	0.030^*
扁桃体和腺样体慢性疾病	红细胞扰动反应（ret DMSO 4.5 h RBC1 SD FSC）	MR Egger	31	-2.615	0.073 (0.001~8.980)	0.295
		Weighted median	31	-0.681	0.506 (0.100~2.555)	0.410
		Inverse variance weighted	31	-1.344	0.261 (0.083~0.819)	0.021^*
扁桃体和腺样体慢性疾病	网织红细胞扰动反应（ret Ciprofloxacin 22 h RET1 Med SSC）	MR Egger	31	-0.808	0.446 (0.138~1.435)	0.186
		Weighted median	31	-0.522	0.593 (0.387~0.908)	0.016^*
		Inverse variance weighted	31	-0.339	0.713 (0.538~0.943)	0.018^*

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