Table 1. Single-Variable MR Results of Prescription Opioid and Nonopioid Pain Medication Use on Risk of MDD and ASRD^a,b.

Exposure	Method	MDD			ASRD
		N SNV	OR (95% CI)	P value	N SNV	OR (95% CI)	P value
Opioid use	IVW	26	1.14 (1.06-1.22)	<.001	23	1.24 (1.07-1.44)	.004
	Weighted median	26	1.18 (1.07-1.30)	<.001	23	1.22 (1.00-1.49)	.05
	MR Egger	26	1.17 (0.92-1.47)	.21	23	1.26 (0.78-2.02)	.36
Salicylic acid use	IVW	27	1.07 (0.98-1.18)	.15	21	1.18 (1.00-1.40)	.05
	Weighted median	27	1.04 (0.92-1.18)	.52	21	1.14 (0.91-1.44)	.25
	MR Egger	27	0.83 (0.66-1.04)	.12	21	0.92 (0.56-1.52)	.75
Anilide use	IVW	29	1.14 (1.01-1.27)	.03	34	1.01 (0.82-1.25)	.93
	Weighted median	29	1.14 (0.97-1.34)	.10	34	0.96 (0.70-1.30)	.77
	MR Egger	29	1.05 (0.67-1.64)	.82	34	0.85 (0.37-1.94)	.70
NSAID use	IVW	29	1.12 (1.02-1.23)	.02	29	1.29 (1.06-1.56)	.01
	Weighted median	29	1.20 (1.05-1.37)	.008	29	1.13 (0.86-1.47)	.38
	MR Egger	29	1.11 (0.78-1.58)	.56	29	1.18 (0.52-2.68)	.70

Abbreviations: ASRD, anxiety and stress-related disorder; GWAS, genome-wide association studies; IVW, inverse variance weighted; MDD, major depression or major depressive disorder (depending on study); MR, mendelian randomization; N SNVs, number of genetic instruments; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; SNV, single-nucleotide variant; SVMR, single-variable mendelian randomization.

^aResults from 2-sample SVMR analysis; main analysis method: outliers identified by MR PRESSO tool, removed; estimated associations reported as OR of outcome per unit increase in log odds of pain medication use.

^bGenetic instruments selected from opioid and nonopioid pain medication use GWASs, selection threshold P less than 5 × 10⁻⁶, pruned at linkage disequilibrium R² less than .001 (10 000 kilobase pair window); N SNV differs across outcomes depending on number of genetic instruments found in outcome GWASs.