The Causal Relationship Between Gastroesophageal Reflux Disease and Chronic Obstructive Pulmonary Disease: A Bidirectional Two-Sample Mendelian Randomization Study

Figures & data

Table 1 Details of the GWASs Data

Traits	Sample Size (Cases/Controls)	Population	Consortium	Web Source
GERD	71,522/261,079	European descent	A meta-analysis of GWAS	https://doi.org/10.1038/s41467-019-11968-2
COPD	16,410/283,589	European	FinnGen	https://r8.finngen.fi/pheno/J10_COPD

Abbreviations: GERD, Gastroesophageal Reflux Disease; COPD, Chronic Obstructive Pulmonary Disease.

Table 2 The Detailed Information of the Instrumental Variables in Each Trait

Traits	SNP	Effect Allele	Other Allele	P-value	Beta	SE	F
COPD	rs143031266	G	A	2.74E-08	0.164683	0.0296348	30.88115523
	rs2273500	C	T	2.19E-11	0.0951338	0.0142143	44.79388539
	rs2904259	C	T	1.97E-08	0.0664499	0.0118358	31.52052393
	rs66694560	A	G	5.19E-10	0.0763852	0.0122937	38.60585883
	rs9270664	A	G	1.25E-08	0.067614	0.0118783	32.40146741
GERD	rs111472920	T	G	4.47E-08	0.0987	0.018	30.06694444
	rs12706746	A	G	4.24E-09	0.0369	0.0063	34.30612245
	rs12939066	T	C	3.13E-11	0.0415	0.0062	44.80359001
	rs13167137	T	G	2.82E-08	−0.0328	0.0059	30.90606148
	rs1473115	T	C	3.95E-10	0.0396	0.0063	39.51020408
	rs15071	T	C	1.01E-08	−0.0428	0.0075	32.56604444
	rs1858828	T	G	3.23E-08	0.0327	0.0059	30.71789716
	rs3072	T	C	1.86E-08	−0.0345	0.0061	31.98736899
	rs62046253	T	C	1.30E-08	−0.0352	0.0062	32.23309053
	rs62442944	T	G	3.49E-08	0.0418	0.0076	30.25
	rs6683411	A	G	4.82E-08	0.0324	0.0059	30.15685148
	rs6710685	T	C	1.96E-09	0.0391	0.0065	36.18485207
	rs6762606	T	C	4.18E-08	−0.0359	0.0065	30.5043787
	rs6809836	A	G	3.70E-09	0.0383	0.0065	34.71928994
	rs6991878	T	C	2.71E-08	−0.0338	0.0061	30.70249933
	rs72704785	A	G	6.81E-09	0.0459	0.0079	33.7575709
	rs7552188	T	C	1.07E-08	0.0413	0.0072	32.90297068
	rs769671	T	C	9.28E-10	−0.0385	0.0063	37.34567901

Abbreviations: SNP, single-nucleotide polymorphism; Beta, the per-allele effect on each trait; SE, standard error; F, F-statistic.

Table 3 Sensitivity Analysis of MR

Exposure	Outcome	nSNPs	Heterogeneity Test		MR-Egger Pleiotropy Test		MR-PRESSO Global Outlier Test
			Q	P-value	Intercept	P-value	RSSobs	P-value	Outlier
GERD	COPD	18	19.275370	0.3129	−0.0191	0.4047	21.77467	0.3400	None
COPD	GERD	6	14.371421	0.0134	0.0141	0.2562	24.56575	0.0367	rs28929474
After remove the outlier
COPD	GERD	5	5.964387	0.2018	−0.0160	0.4564	9.919114	0.2673	None

Abbreviations: GERD, Gastroesophageal Reflux Disease; COPD, Chronic Obstructive Pulmonary Disease; SNP, single-nucleotide polymorphism; MR-PRESSO, MR pleiotropy residual sum and outlier.

Figure 1 Estimated causal effect of GERD on COPD using different MR methods.

Abbreviations: SNP, single-nucleotide polymorphism; pval, p value; OR, Odds Ratio; CI, Confidence Interval.

Figure 2 Estimated causal effect of COPD on GERD using different MR methods.

Abbreviations: SNP, single-nucleotide polymorphism; pval, p value; OR, Odds Ratio; CI, Confidence Interval.