Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis

Table 1 Number of single-nucleotide polymorphisms screened in each step

ID exposure	Panel	Immune traits	Number of SNPs after LD	Number of SNPs after F > 10	Number of final IVs
Ebi-a-GCST90001433	B cell	IgD- CD27-% lymphocyte	18	18	18
Ebi-a-GCST90001706	B cell	BAFF-R on IgD + CD38- naive	29	29	28
Ebi-a-GCST90001762	B cell	CD20 on IgD +	23	23	19
Ebi-a-GCST90001790	B cell	CD25 on memory B cell	27	27	24
Ebi-a-GCST90001830	B cell	BAFF-R on CD20-	14	14	14
Ebi-a-GCST90001793	B cell	CD25 on sw mem	21	21	20
Ebi-a-GCST90001809	B cell	CD38 on CD20-	20	20	19
Ebi-a-GCST90002110	Myeloid cell	HLA DR on CD33dim HLA DR + CD11b +	24	24	23
Ebi-a-GCST90001954	Myeloid cell	CD33 on basophil	23	23	22
Ebi-a-GCST90001952	Myeloid cell	CD33 on Mo MDSC	21	21	21
Ebi-a-GCST90001951	Myeloid cell	CD33 on CD66b + + myeloid cell	19	19	18
Ebi-a-GCST90001521	Myeloid cell	CD33 bright HLA DR + CD14 dim% CD33 bright HLA DR +	26	26	25
Ebi-a-GCST90001953	Myeloid cell	CD33 on CD33 dim HLA DR-	21	21	19
Ebi-a-GCST90001955	Myeloid cell	CD33 on Im MDSC	25	25	22
Ebi-a-GCST90002031	Treg	CD39 on CD39 + secreting Treg	24	24	23
Ebi-a-GCST90001901	Treg	CD28 on CD39 + resting Treg	23	23	22
Ebi-a-GCST90001688	Treg	CD28 + CD45 RA + CD8 bright% T cell	112	91	88
Ebi-a-GCST90001630	TBNK	CD8 bright NKT AC	27	27	26
Ebi-a-GCST90002076	TBNK	SSC-A on NK	24	24	23
Ebi-a-GCST90002014	cDC	CCR2 on CD62 L + myeloid DC	15	15	14

TBNK: T cells, B cells, and natural killer cells; ID: Identification; cDC: Conventional dendritic cells; CD: Cluster of differentiation; DR: Dweller region; AC: Absolute count; SSC-A: Side scatter-A; LD: Linkage disequilibrium; BAFF: B-cell-activating factor; HLA: Human leukocyte antigen; MDSC: Myeloid-derived suppressor cells; NKT: Natural killer T cells; NK: Natural killer; CCR2: C-C motif chemokine receptor 2; SNPs: Single-nucleotide polymorphisms; IVs: Instrumental variables.

Table 2 Forward mendelian randomization sensitivity analysis

Exposure panel	Exposure traits	Inverse variance weighted		MR-Egger
		Q value	P value	Intercept	P value
B cell	IgD- CD27-% lymphocyte	11.20	0.846	0.008	0.707
B cell	BAFF-R on IgD+ CD38- naive	19.98	0.831	0.002	0.880
B cell	CD20 on IgD+	18.76	0.407	-0.004	0.662
B cell	CD25 on memory B cell	21.52	0.549	-0.002	0.854
B cell	BAFF-R on CD20-	9.74	0.715	-0.005	0.795
B cell	CD25 on sw mem	17.72	0.541	0.004	0.771
B cell	CD38 on CD20-	14.73	0.680	0.012	0.521
Myeloid cell	HLA DR on CD33dim HLA DR+ CD11b+	25.66	0.266	-0.011	0.303
Myeloid cell	CD33 on basophil	29.56	0.101	0.014	0.248
Myeloid cell	CD33 on Mo MDSC	23.26	0.276	-0.007	0.490
Myeloid cell	CD33 on CD66b+ myeloid cell	18.20	0.376	-0.029	0.065
Myeloid cell	CD33 bright HLA DR+ CD14 dim% CD33 bright HLA DR+	29.63	0.197	0.011	0.294
Myeloid cell	CD33 on CD33 dim HLA DR-	18.45	0.427	0.018	0.184
Myeloid cell	CD33 on Im MDSC	30.80	0.077	0.013	0.354
Treg	CD39 on CD39+ secreting Treg	10.76	0.978	-0.005	0.554
Treg	CD28 on CD39+ resting Treg	21.59	0.423	0.013	0.220
Treg	CD28+ CD45 RA+ CD8 bright% T cell	80.46	0.676	0.009	0.252
TBNK	CD8 bright NKT AC	25.19	0.452	-0.014	0.225
TBNK	SSC-A on NK	27.35	0.198	0.004	0.771
cDC	CCR2 on CD62L+ myeloid DC	9.06	0.768	0.011	0.547

TBNK: T cells, B cells, and natural killer; cDC: Conventional dendritic cells; CD: Cluster of Differentiation; AC: Absolute count; BAFF: B-cell-activating factor; HLA: Human leukocyte antigen; MDSC: Myeloid-derived suppressor cells; NKT: Natural killer T cells; NK: Natural killer; CCR2: C-C motif chemokine receptor 2; SNPs: Single-nucleotide polymorphisms; IVs: Instrumental variables; MR: Mendelian randomization.

Table 3 Number of Single-nucleotide polymorphisms screened in each step

ID exposure	Number of SNPs after LD	Number of SNPs after F > 10	Number of final IVs
Finn-b-CIRRHOSIS_BROAD	31	31	31

ID: Identification; LD: Linkage disequilibrium; SNPs: Single-nucleotide polymorphisms; IVs: Instrumental variables.

Table 4 Reverse mendelian randomization sensitivity analysis

Outcome panel	Outcome traits	Inverse variance weighted		MR-Egger
		Q value	P value	intercept	P value
B cell	IgD+ CD38 bright AC	35.51	0.224	-0.014	0.401
B cell	IgD+ CD38 dim AC	30.73	0.429	-0.030	0.068
B cell	IgD+ AC	33.15	0.316	-0.028	0.094
B cell	Naive-mature B cell AC	27.47	0.599	-0.022	0.160
B cell	IgD+ CD24- AC	29.82	0.475	-0.019	0.250
cDC	CD62L- plasmacytoid DC AC	29.39	0.497	0.029	0.075
Myeloid cell	Im MDSC AC	29.23	0.506	0.019	0.249
Myeloid cell	Im MDSC% CD33 dim HLA DR- CD66b-	24.09	0.768	0.009	0.568
Myeloid cell	CD33- HLA DR+ AC	30.39	0.446	-0.004	0.790
TBNK	CD4+% leukocyte	16.12	0.982	0.007	0.670
TBNK	CD3- lymphocyte% leukocyte	17.10	0.971	0.013	0.443
Treg	CD28+ CD45RA- CD8 dim AC	37.39	0.166	0.000	0.997
B cell	CD20 on CD24+ CD27+	22.52	0.834	0.026	0.231
B cell	CD20 on sw mem	32.59	0.341	0.020	0.381
TBNK	FSC-A on B cell	25.61	0.695	0.017	0.345
Monocyte	CX3CR1 on monocyte	39.69	0.111	0.002	0.891
Monocyte	CX3CR1 on CD14- CD16+ monocyte	19.80	0.922	0.008	0.641
TBNK	SSC-A on B cell	32.70	0.336	-0.003	0.844
Treg	CD8 on CD28- CD8 bright	37.59	0.106	-0.003	0.877

TBNK: T cells, B cells, and natural killer cells; DC: Dendritic cells; AC: Absolute count; FSC-A: Forward scatter-A; SSC-A: Side scatter-A; CD: Cluster of differentiation.