Table 2. Multivariable MR Results of Prescription Opioid and Nonopioid Pain Medications Use on Risk of MDD and ASRD^a,b.

MV exposures	Methods	MDD			ASRD
		No. of SNVs	OR (95% CI)	P value	No. of SNVs	OR (95% CI)	P value
Opioid use	MV IVW	92	1.14 (1.04-1.25)	.005	86	1.30 (1.08-1.56)	.006
	MV Egger	92	1.13 (1.02-1.26)	.02	86	1.18 (0.95-1.46)	.13
NSAID use	MV IVW	92	0.98 (0.84-1.15)	.81	86	1.37 (0.99-1.90)	.06
	MV Egger	92	0.97 (0.82-1.15)	.72	86	1.23 (0.87-1.73)	.24
Salicylic acid use	MV IVW	92	0.99 (0.89-1.11)	.88	86	0.96 (0.76-1.21)	.70
	MV Egger	92	0.98 (0.87-1.11)	.76	86	0.84 (0.64-1.10)	.21
Anilide use	MV IVW	92	1.07 (0.89-1.29)	.46	86	0.71 (0.49-1.03)	.07
	MV Egger	92	1.06 (0.87-1.28)	.56	86	0.64 (0.43-0.94)	.02

Abbreviations: ASRD, anxiety and stress-related disorder; GWAS, genome-wide association studies; IVW, inverse variance weighted MR; MDD, major depression or major depressive disorder (depending on study used in GWAS); MR, mendelian randomization; MV IVW, multivariable inverse variance weighted; MVMR, multivariable mendelian randomization; N SNV, number of SNVs; OR, odds ratio; SNV, single-nucleotide variant.

^aResults from outlier-corrected 2-sample multivariable MR analysis, 2 multivariable complementary methods reported; main analysis method: estimates reported as OR of psychiatric outcome per unit increase in log odds of pain medication use exposure, accounting for other pain medication uses.

^bInstruments selected from opioid and nonopioid GWASs, selection threshold P less than 5 × 10⁻⁶, pruned at linkage disequilibrium R² less than 0.001 (10 000 kilobase pair window); outliers identified by MR PRESSO tool, removed; N SNVs differs across outcomes depending on number of instrument SNVs found in psychiatric outcome GWASs.