Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

Table 1 Genome-wide association study data sources and information included in the current study

Trait	Phenotype	Sample size	SNPs	Ancestry	Consortium	Link
Educational attainment	Age completed full time education	307897	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-6134/
Manual labor	Job involves heavy manual or physical work	263615	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-2002/
Household income	Average total household income before tax	397751	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-7408/
Residential environment	Type of accommodation lived in: Apartment, duplex, or condominium	360088	13586555	European	Neale Lab	https://gwas.mrcieu.ac.uk/datasets/ukb-d-670_2/
	Type of accommodation lived in: A house or bungalow	360088	13586555	European	Neale Lab	https://gwas.mrcieu.ac.uk/datasets/ukb-d-670_1/
Regional deprivation	Townsend Deprivation Index at recruitment	462464	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-10011/
Leisure or social activities	Leisure/social activities: Pub or social club	461369	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-4171/
	Leisure/social activities: Sports club or gym	461369	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-4000/
Esophageal diseases	Gastroesophageal reflux disease	602604	2320781	European	Ong JS	https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90000514/
	Barrett’s esophagus	56429	2320520	European	Ong JS	https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90000515/
Metabolic factors	Body mass index	322154	2554668	European	GIANT	https://gwas.mrcieu.ac.uk/datasets/ieu-a-835/
Psychological factors	Major depressive disorder	173005	13554550	European	PGC	https://gwas.mrcieu.ac.uk/datasets/ieu-a-1188/
Lifestyle factors	Cigarettes smoked per day	249752	12003613	European	GSCAN	https://gwas.mrcieu.ac.uk/datasets/ieu-b-142/
	Drinks per week	335394	11887865	European	GSCAN	https://gwas.mrcieu.ac.uk/datasets/ieu-b-73/
	Sleep duration	460099	9851867	European	MRC-IEU	https://gwas.mrcieu.ac.uk/datasets/ukb-b-4424/

GSCAN: Genome-wide association study and Sequencing Consortium of Alcohol and Nicotine Use; MRC-IEU: The Medical Research Council Integrative Epidemiology Unit; PGC: Psychiatric Genomics Consortium; SNPs: Single nucleotide polymorphisms.

Table 2 Univariate Mendelian randomization analysis for genetically causal associations of socioeconomic traits with gastroesophageal reflux disease risk

Exposure	Outcome	F statistic	SNP	IVW OR (95%CI)	P value	Weighted median OR (95%CI)	P value	MR-Egger OR (95%CI)	P value
Age completed full time education	GERD	21.564	27	0.23 (0.18, 0.29)	3.120E-37	0.27 (0.21, 0.35)	3.890E-24	0.26 (0.08, 0.83)	0.032
Job involves heavy manual or physical work	GERD	15.312	10	2.62 (1.90, 3.63)	5.470E-09	2.35 (1.66, 3.34)	1.760E-06	0.37 (0.07, 1.83)	0.257
Average total household income before tax	GERD	16.722	9	0.45 (0.34, 0.59)	1.090E-08	0.55 (0.40, 0.76)	< 0.001	0.83 (0.07, 10.68)	0.891
Type of accommodation lived in: Apartment, duplex, or condominium	GERD	21.654	0	NA	NA	NA	NA	NA	NA
Type of accommodation lived in: House or bungalow	GERD	17.211	0	NA	NA	NA	NA	NA	NA
TDI at recruitment	GERD	22.719	6	2.77 (1.80, 4.28)	3.770E-06	2.32 (1.42, 3.79)	0.001	0.12 (0.01, 1.95)	0.211

95%CI: 95% confidence interval; GERD: Gastroesophageal reflux disease; IVW: Inverse variance weighted; MR: Mendelian randomization; NA: Not available; OR: Odds ratio; SNPs: Single nucleotide polymorphisms; TDI: Townsend Deprivation Index.

Table 3 Univariate Mendelian randomization analysis for genetically causal associations of socioeconomic traits with Barrett’s esophagus risk

Exposure	Outcome	F statistic	SNP	IVW OR (95%CI)	P value	Weighted median OR (95%CI)	P value	MR-Egger OR (95%CI)	P value
Age completed full time education	BE	32.511	12	0.11 (0.05, 0.22)	7.830E-10	0.14 (0.05, 0.36)	7.010E-05	0.240 (0.02, 3.66)	0.328
Job involves heavy manual or physical work	BE	21.688	11	4.59 (2.15, 9.82)	8.370E-05	2.90 (1.18, 7.12)	0.020	0.480 (0.01, 47.14)	0.760
Average total household income before tax	BE	12.432	17	0.43 (0.23, 0.80)	0.007	0.51 (0.25, 1.03)	0.061	0.670 (0.05, 9.53)	0.771
Type of accommodation lived in: Apartment, duplex, or condominium	BE	17.781	0	NA	NA	NA	NA	NA	NA
Type of accommodation lived in: House or bungalow	BE	19.785	0	NA	NA	NA	NA	NA	NA
TDI at recruitment	BE	17.710	8	1.23 (0.51, 2.96)	0.648	0.92 (0.31, 2.71)	0.875	0.002 (0.00, 4.11)	0.162

BE: Barrett’s esophagus; 95%CI: 95% confidence interval; IVW: Inverse variance weighted; MR: Mendelian randomization; NA: Not available; OR: Odds ratio; SNPs: Single nucleotide polymorphisms; TDI: Townsend Deprivation Index.

Table 4 Multivariate separate-sample Mendelian randomization analysis of the effect of socioeconomic traits

Exposure	Outcome	OR (95%CI)	P value	Mediation effect
Age completed full time education	GERD	0.27 (0.23, 0.33)	6.410E-46	10.83%
Age completed full time education	BE	0.13 (0.08, 0.23)	2.140E-13	10.58%
Age completed full time education	BE	0.11 (0.07, 0.20)	2.900E-14	3.50%
Age completed full time education	BE	0.14 (0.08, 0.24)	1.290E-13	6.88%
Average total household income before tax	GERD	0.36 (0.30, 0.44)	3.240E-23	9.75%

BE: Barrett’s esophagus; 95%CI: 95% confidence interval; GERD: Gastroesophageal reflux disease; OR: Odds ratio.