Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

Table 1 Supplementary and sensitivity analyses for causality from blood metabolites on gastroesophageal reflux disease

Metabolites	n	MR analysis			Heterogeneity		Pleiotropy
		Method	OR (95%CI)	P value	Q	P value	Intercept	P value
Amino acid
Tryptophan	162	ME	0.72 (0.37-1.40)	0.34	160	0.58	0.002	0.07
		WM	1.42 (1.11-1.82)	0.006
Kynurenine	33	ME	1.19 (0.78-1.81)	0.44	31	0.88	0.002	0.96
		WM	1.16 (0.90-1.48)	0.24
Levulinate (4-oxovalerate)	52	ME	0.96 (0.73-1.27)	0.80	50	0.94	0.002	0.15
		WM	0.86 (0.67-1.09)	0.20
Indoleacetate	16	ME	0.79 (0.60-1.05)	0.13	14	0.74	0.003	0.72
		WM	0.83 (0.67-1.04)	0.11
Cofactors and Vitamin
Ascorbate (Vitamin C)	12	ME	1.06 (0.89-1.25)	0.54	10	0.48	0.006	0.94
		WM	1.05 (0.98-1.13)	0.17
Lipid
Stearate (18:0)	31	ME	0.82 (0.51-1.32)	0.43	29	0.49	0.003	0.51
		WM	0.78 (0.60-1.01)	0.06
1-linoleoylglycerophosphoethanolamine	13	ME	1.16 (0.80-1.68)	0.44	11	0.85	0.004	0.99
		WM	1.24 (1.03-1.50)	0.03
1-stearoylglycerol (1-monostearin)	20	ME	1.42 (0.62-3.25)	0.42	18	0.49	0.006	0.90
		WM	1.16 (0.90-1.50)	0.25
1-palmitoylglycerol (1-monopalmitin)	11	ME	0.88 (0.48-1.60)	0.68	9	0.89	0.005	0.27
		WM	1.09 (0.83-1.43)	0.54
7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca)	11	ME	1.12 (0.52-2.41)	0.78	9	0.36	0.006	0.23
		WM	0.70 (0.48-1.01)	0.06
Butyrylcarnitine	39	ME	1.06 (0.99-1.15)	0.11	37	0.30	0.002	0.26
		WM	1.07 (1.00-1.14)	0.04
2-palmitoylglycerophosphocholine*	21	ME	0.91 (0.72-1.14)	0.41	19	0.76	0.002	0.50
		WM	0.97 (0.79-1.20)	0.80
10-nonadecenoate (19:1n9)	7	ME	0.95 (0.60-1.50)	0.83	5	0.52	0.006	0.19
		WM	1.27 (1.00-1.61)	0.05
1-stearoylglycerophosphocholine	9	ME	1.55 (0.85-2.83)	0.20	7	0.87	0.006	0.53
		WM	1.30 (1.01-1.67)	0.04
Adrenate (22:4n6)	11	ME	0.75 (0.50-1.12)	0.19	9	0.20	0.005	0.66
		WM	0.74 (0.60-0.91)	0.004
Nucleotide
Guanosine	11	ME	1.31 (1.06-1.64)	0.04	9	0.99	0.005	0.16
		WM	1.16 (1.05-1.29)	0.005
Xenobiotics
p-acetamidophenylglucuronide	32	ME	1.00 (0.99-1.00)	0.41	30	0.25	0.004	0.60
		WM	1.00 (0.99-1.00)	0.75
Unknow
X-09108	9	ME	1.31 (0.72-2.37)	0.41	7	0.71	0.005	0.61
		WM	1.31 (0.89-1.93)	0.17
X-11247	18	ME	0.92 (0.78-1.10)	0.37	16	0.68	0.004	0.82
		WM	0.91 (0.83-0.99)	0.03
X-11452	5	ME	1.02 (0.67-1.56)	0.93	3	0.45	0.008	0.58
		WM	1.15 (0.97-1.36)	0.10
X-11787	33	ME	0.84 (0.64-1.12)	0.25	31	0.94	0.002	0.84
		WM	0.89 (0.72-1.11)	0.31
X-12007	18	ME	1.10 (1.03-1.17)	0.01	16	0.68	0.003	0.39
		WM	1.07 (1.01-1.13)	0.02
X-12063	21	ME	1.06 (0.98-1.16)	0.16
		WM	1.10 (1.03-1.17)	0.004	19	0.30	0.002	0.60
X-12456	21	ME	1.26 (1.07-1.49)	0.01	19	0.86	0.003	0.09
		WM	1.10 (0.99-1.22)	0.07
X-12786	12	ME	0.95 (0.78-1.14)	0.58	10	0.87	0.003	0.48
		WM	0.91 (0.80-1.05)	0.20

MR: Mendelian randomization; ME: MR-egger; WM: Weighted median; CI: Confidence interval; OR: Odd ratio.