Causal relationship between Helicobacter pylori infection and IgA nephropathy: a bidirectional two-sample mendelian randomization study

Figures & data

Figure 1. An investigation of the causal relationship between H. pylori infection and IgAN.

Figure 2. Schematic representation of the bidirectional MR study on the causal relationship between H. pylori infection and IgAN. IVs: instrument variants; SNP: single-nucleotide polymorphisms; IgAN, IgA nephropathy.

Table 1. Details of the GWAS data in this study.

Exposure and Outcome	Source	Sample size	Ancestry	Year	Numbers of SNPs	Access Link
Anti-H. pylori IgG	UKB	8735	European	2020	9,170,312	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006910
H. pylori CagA antibody	UKB	985	European	2020	9,165,056	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006911
H. pylori CAT antibody	UKB	1558	European	2020	9,167,570	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006912
H. pylori GroEL antibody	UKB	2716	European	2020	9,172,299	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006913
H. pylori OMP antibody	UKB	2640	European	2020	9,167,440	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006914
H. pylori UREA antibody	UKB	2251	European	2020	9,170,248	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006915
H. pylori VacA antibody	UKB	1571	European	2020	9,178,635	https://gwas.mrcieu.ac. uk/datasets/ebi-a-GCST90006916
IgAN	FinnGen; UKB;BBJ	477,784	European	2021	24,182,646	https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90018866

SNP: single-nucleotide polymorphisms; IgAN: IgA nephropathy.

Table 2. Results of the sensitivity analysis between H. pylori infection and IgAN estimated by the forward MR method.

Exposure	Heterogeneity							Horizontal pleiotropy
	MR-Egger		IVW		MR-Egger regression			MR-PRESSO			steiger test
	Q	I^2	Q	I^2	Intercept	SE	p	p	Raw p	Outlier-corrected	pval	dir
Anti-H. pylori IgG	0.501	0%	0.564	0%	0.007	0.014	0.611	0.571	0.078	NA	5.063E-69	TRUE
H. pylori CagA antibody	0.387	5.6%	0.345	8.9%	0.013	0.010	0.211	0.349	0.934	NA	4.165E-129	TRUE
H. pylori CAT antibody	0.009	55.1%	0.011	52.5%	−0.008	0.015	0.587	0.137	0.952	NA	5.906E-75	TRUE
H. pylori GroEL antibody	0.149	37.2%	0.121	34.9%	0.020	0.017	0.294	0.131	0.931	NA	9.891E-39	TRUE
H. pylori OMP antibody	0.236	20.0%	0.264	16.9%	0.009	0.012	0.500	0.236	0.228	NA	2.251E-81	TRUE
H. pylori UREA antibody	0.589	0%	0.571	0%	−0.011	0.010	0.279	0.585	0.887	NA	4.816E-120	TRUE
H. pylori VacA antibody	0.498	0%	0.354	7.8%	−0.017	0.009	0.075	0.367	0.094	NA	3.779E-138	TRUE

Table 3. Forward MR of serum H. pylori antibodies with IgAN.

Exposure	Method	SNPs		OR(95%CI)	p-Value
Anti-H. pylori IgG	Inverse variance weighted	13		0.834(0.685–1.015)	0.070
	MR Egger	13		0.739(0.451–1.210)	0.255
	Weighted median	13		0.903(0.690–1.182)	0.456
H. pylori CagA antibody	Inverse variance weighted	20		0.999(0.973–1.025)	0.933
	MR Egger	20		0.964(0.907–1.023)	0.242
	Weighted median	20		1.016(0.980–1.054)	0.387
H. pylori CAT antibody	Inverse variance weighted	14		1.002(0.950–1.057)	0.951
	MR Egger	14		1.030(0.920–1.054)	0.614
	Weighted median	14		1.012(0.953–1.074)	0.704
H. pylori GroEL antibody	Inverse variance weighted	9		1.003(0.929–1.084)	0.929
	MR Egger	9		0.919(0.775–1.089)	0.362
	Weighted median	9		0.990(0.905–1.083)	0.832
H. pylori OMP antibody	Inverse variance weighted	15		0.969(0.923–1.018)	0.208
	MR Egger	15		0.934(0.831–1.049)	0.268
	Weighted median	15		0.981(0.918–1.049)	0.581
H. pylori UREA antibody	Inverse variance weighted	22		0.998(0.962–1.034)	0.891
	MR Egger	22		1.044(0.956–1.139)	0.349
	Weighted median	22		1.009(0.960–1.060)	0.730
H. pylori VacA antibody	Inverse variance weighted	23		1.027(0.997–1.058)	0.081
	MR Egger	23		1.081(1.017–1.149)	0.020
	Weighted median	23		1.015(0.976–1.055)	0.454

SNP: single-nucleotide polymorphisms; OR: odds ratio; LCl: lower confidence interval; UCI: upper confidence interval; IgAN: IgA nephropathy.

Table 4. Results of the sensitivity analysis between H. pylori infection and IgAN estimated by the reverse MR method.

Exposure	Heterogeneity						Horizontal pleiotropy
	MR-Egger		IVW		MR-Egger regression			MR-PRESSO
	Q	I^2	Q	I^2	Intercept	SE	p	p	Raw p	Outlier-corrected
Anti-H. pylori IgG	0.195	18.6%	0.118	24.7%	−0.009	0.005	0.085	0.100	0.761	NA
H. pylori CagA antibody	0.853	0%	0.880	0%	−0.012	0.031	0.691	0.878	0.946	NA
H. pylori CAT antibody	0.576	0%	0.596	0%	0.018	0.023	0.438	0.623	0.388	NA
H. pylori GroEL antibody	0.060	31.6%	0.057	31.6%	0.021	0.215	0.330	0.054	0.821	NA
H. pylori OMP antibody	0.857	0%	0.753	0%	0.033	0.018	0.086	0.748	0.934	NA
H. pylori UREA antibody	0.850	0%	0.750	0%	0.035	0.019	0.091	0.754	0.227	NA
H. pylori VacA antibody	0.156	22.0%	0.086	28.4%	0.050	0.028	0.081	0.090	0.904	NA

Table 5. Reverse MR of serum H. pylori antibodies with IgAN.

Exposure	Method	SNPs		OR(95%CI)	p-Value
Anti-H. pylori IgG	Inverse variance weighted	28		0.992(0.945–1.042)	0.759
	MR Egger	28		1.092(0.974–1.225)	0.145
	Weighted median	28		0.968(0.906–1.033)	0.328
H. pylori CagA antibody	Inverse variance weighted	27		0.992(0.745–1.320)	0.955
	MR Egger	27		1.137(0.551–2.347)	0.732
	Weighted median	27		0.992(0.745–1.320)	0.796
H. pylori CAT antibody	Inverse variance weighted	28		1.099(0.882–1.369)	0.402
	MR Egger	28		0.903(0.529–1.542)	0.712
	Weighted median	28		1.027(0.747–1.413)	0.869
H. pylori GroEL antibody	Inverse variance weighted	28		1.024(0.836–1.254)	0.820
	MR Egger	28		0.815(0.497–1.336)	0.425
	Weighted median	28		1.045(0.817–1.336)	0.727
H. pylori OMP antibody	Inverse variance weighted	28		0.993(0.836–1.181)	0.940
	MR Egger	28		0.696(0.454–1.067)	0.108
	Weighted median	28		0.960(0.759–1.213)	0.730
H. pylori UREA antibody	Inverse variance weighted	28		1.111(0.923–1.337)	0.267
	MR Egger	28		0.766(0.486–1.206)	0.260
	Weighted median	28		0.958(0.741–1.238)	0.742
H. pylori VacA antibody	Inverse variance weighted	27		0.984(0.753–1.284)	0.903
	MR Egger	27		0.567(0.297–1.082)	0.098
	Weighted median	27		1.066(0.756–1.504)	0.714

OR: odds ratio; LCl: lower confidence interval; UCI: upper confidence interval; IgAN: IgA nephropathy.

Data availability statement

The data we used are publicly available summary statistics and can be obtained upon reasonable request.