Table 1.

Single variable and multivariable MR results of the genetic liability of alcohol, cannabis and lifetime smoking exposures on COVID-19 outcomes.

	Single-variable MR					Multivariable MR
	N SNPs	OR	95% CI Lower	95% CI Upper	P-value	N SNPs	MV OR	95% CI Lower	95% CI Upper	P-value
Very severe respiratory confirmed COVID-19 vs. population
Tobacco smoking	91	2.69	1.42	5.10	0.002	111	2.72	1.27	5.82	0.010
Cannabis use	28	1.17	0.92	1.50	0.207	114	1.03	0.76	2.80	0.856
CUD	22	0.97	0.82	1.15	0.748	111	1.02	0.86	1.22	0.805
Drinks per week	22	1.39	0.52	3.74	0.511	114	0.83	0.33	2.30	0.698
AUD	9	0.91	0.75	1.11	0.344	111	0.95	0.82	1.09	0.442
Hospitalized COVID-19 vs. not hospitalized COVID-19
Tobacco smoking	91	3.44	1.72	6.87	4.60E−04	111	3.61	1.63	8.01	0.002
Cannabis use	28	0.87	0.68	1.11	0.270	114	1.02	0.77	2.78	0.883
CUD	21	1.07	0.91	1.25	0.404	111	1.04	0.87	1.25	0.627
Drinks per week	21	0.69	0.27	1.76	0.432	114	0.37	0.15	1.45	0.034
AUD	9	0.83	0.69	0.99	0.035	111	0.94	0.81	1.10	0.451
Hospitalized COVID-19 vs. population
Tobacco smoking	91	3.49	2.23	5.44	3.74E−08	111	3.61	2.19	5.95	4.92E−07
Cannabis use	28	0.99	0.85	1.16	0.887	114	1.00	0.83	2.73	0.964
CUD	21	0.99	0.90	1.10	0.871	111	1.01	0.90	1.13	0.915
Drinks per week	21	1.01	0.57	1.81	0.964	114	0.59	0.32	1.80	0.079
AUD	8	0.94	0.82	1.08	0.375	111	0.98	0.89	1.07	0.633
COVID-19 vs. population
Tobacco smoking	91	1.21	0.97	1.52	0.095	111	1.25	0.95	1.64	0.104
Cannabis use	28	1.11	1.02	1.21	0.022	114	1.04	0.95	2.83	0.404
CUD	21	0.98	0.93	1.03	0.436	111	0.98	0.92	1.04	0.411
Drinks per week	21	1.09	0.81	1.47	0.565	114	0.93	0.68	2.52	0.622
AUD	8	1.08	1.00	1.16	0.039	111	1.03	0.98	1.08	0.310

Notes: Results from two sample SVMR inverse-variance weighted MR analysis; outliers identified by MR PRESSO global test and, for MVMR, MV MR Lasso penalization were removed; estimated associations reported as odds ratios with 95% confidence intervals. Boldface indicates statistical significance after correction for multiple comparisons (P < 0.0025). Genetic instruments selected from five GWASs, selection threshold P < 5 × 10⁻⁸ or P < 5 × 10⁻⁶ (CUD and AUD), clumped at linkage disequilibrium (LD) r² = 0.001 (10 000 kilobase pair window); N SNPs differs across outcomes depending on number of genetic instruments found in outcome GWASs. CUD cannabis use disorder, AUD alcohol use disorder, COVID-19 coronavirus 2019, MR Mendelian randomization, GWAS genome wide association study, N SNPs number of single-nucleotide polymorphism (genetic instruments), OR odds ratio, CI confidence interval.