Table 1.

Single Variable MR Results of the Genetic Liability of Alcohol, Cannabis and Lifetime Smoking Exposures on COVID-19 Outcomes

Outcome	Exposure	N SNPs	Odds Ratio	CI Lower Bound	CI Upper Bound	P-value
Hospitalized v not hospitalized	Lifetime smoking	91	1.710	0.689	4.240	0.247
	Cannabis use	26	1.104	0.888	1.371	0.373
	Cannabis use disorder	38	0.991	0.744	1.320	0.949
	Drinks per week	71	1.229	0.490	3.079	0.660
	Alcohol use disorder	10	0.897	0.700	1.151	0.393
Hospitalized v population (European)	Lifetime smoking	91	4.039	2.335	6.985	5.93E-07
	Cannabis use	25	1.079	0.929	1.252	0.320
	Cannabis use disorder	37	1.032	0.829	1.285	0.780
	Drinks per week	70	0.906	0.473	1.733	0.765
	Alcohol use disorder	9	0.931	0.779	1.113	0.434
Very severe hospitalized v not hospitalized	Lifetime smoking	91	3.097	1.883	5.092	8.40E-06
	Cannabis use	25	0.937	0.454	1.933	0.860
	Cannabis use disorder	38	1.010	0.862	1.183	0.901
	Drinks per week	71	0.882	0.505	1.540	0.658
	Alcohol use disorder	10	0.921	0.789	1.076	0.302
COVID-19 v self-reported negative	Lifetime smoking	91	0.852	0.596	1.217	0.379
	Cannabis use	25	1.031	0.957	1.112	0.420
	Cannabis use disorder	38	0.940	0.822	1.076	0.370
	Drinks per week	70	0.870	0.608	1.245	0.447
	Alcohol use disorder	10	1.128	1.039	1.226	0.004
COVID-19 v population (European)	Lifetime smoking	91	1.187	0.856	1.647	0.304
	Cannabis use	25	1.019	0.945	1.098	0.627
	Cannabis use disorder	38	0.964	0.843	1.101	0.588
	Drinks per week	70	0.799	0.554	1.154	0.232
	Alcohol use disorder	10	1.102	0.991	1.225	0.073
COVID-19 v population	Lifetime smoking	91	1.144	0.845	1.550	0.383
	Cannabis use	25	1.046	0.983	1.114	0.154
	Cannabis use disorder	38	0.974	0.870	1.090	0.644
	Drinks per week	71	0.818	0.579	1.156	0.254
	Alcohol use disorder	10	1.061	0.972	1.158	0.188
Predicted COVID-19 v self-reported negative	Lifetime smoking	91	0.887	0.476	1.653	0.705
	Cannabis use	24	1.093	0.963	1.241	0.171
	Cannabis use disorder	37	1.036	0.802	1.339	0.787
	Drinks per week	71	0.664	0.332	1.327	0.246
	Alcohol use disorder	10	1.126	0.965	1.314	0.131

Abbreviations: MR, mendelian randomization; GWAS, genome wide association study; N SNPs, number of single-nucleotide polymorphism (genetic instruments); OR, odds ratio; CI, confidence interval.

^aResults from two sample SVMR inverse-variance weighted MR analysis; outliers identified by MR PRESSO tool were removed; estimated associations reported as odds ratios with 95% confidence intervals. Boldface indicates conventional statistical significance (P<0.05).

^bGenetic instruments selected from 5 GWASs, selection threshold P < 5 × 10⁻⁸ or P < 5 × 10⁻⁶, clumped at linkage disequilibrium (LD) r² = .001 (10 000 kilobase pair window); N SNPs differs across outcomes depending on number of genetic instruments found in outcome GWASs.