Table 2.

Single variable and multivariable MR results of the genetic liability of alcohol, cannabis and lifetime smoking exposures on asthma-related respiratory infections.

Outcome	Exposure	Single-variable MR					Multivariable MR
		N SNPs	OR	95% CI Lower	95% CI Upper	P-value	N SNPs	OR	95% CI Lower	95% CI Upper	P-value
Asthma related acute respiratory infections
	Tobacco smoking	116	2.06	1.39	3.05	3.15E−04	137	2.07	1.31	3.26	0.002
	Cannabis Use	35	1.07	0.98	1.16	0.128	142	1.03	0.88	1.22	0.704
	CUD	27	1.10	1.03	1.19	0.007	137	1.01	0.92	1.11	0.835
	Drinks Per Week	32	0.92	0.56	1.53	0.757	142	1.06	0.65	1.72	0.816
	AUD	11	1.04	0.93	1.17	0.456	137	1.01	0.93	1.10	0.826
Asthma related infections
	Tobacco smoking	115	2.31	1.61	3.31	5.69E−06	127	2.15	1.45	3.17	1.21E−04
	Cannabis Use	35	1.02	0.94	1.09	0.672	142	1.06	0.91	1.23	0.484
	CUD	27	1.08	1.00	1.16	0.040	127	0.98	0.91	1.07	0.662
	Drinks Per Week	32	0.94	0.61	1.44	0.773	142	0.96	0.61	1.49	0.845
	AUD	11	1.04	0.95	1.13	0.385	127	1.03	0.96	1.10	0.358
Asthma-related pneumonia
	Tobacco smoking	116	2.52	1.59	3.97	7.29E−05	138	3.64	2.16	6.11	1.07E−06
	Cannabis Use	36	0.95	0.85	1.06	0.382	136	1.07	0.90	1.27	0.500
	CUD	27	1.07	0.98	1.18	0.120	138	0.95	0.85	1.06	0.380
	Drinks Per Week	31	1.47	0.83	2.59	0.187	136	1.09	0.61	1.93	0.272
	AUD	11	1.09	0.97	1.21	0.132	138	0.99	0.90	1.08	0.755
Asthma-related pneumonia or sepsis
	Tobacco smoking	116	2.54	1.61	4.02	6.54E−05	138	3.66	2.17	6.16	1.04E−06
	Cannabis Use	35	0.96	0.87	1.07	0.472	141	1.08	0.90	1.31	0.401
	CUD	27	1.07	0.98	1.18	0.122	138	0.95	0.85	1.07	0.399
	Drinks Per Week	32	1.85	1.04	3.26	0.035	141	1.15	0.66	2.00	0.616
	AUD	11	1.09	0.97	1.21	0.138	138	0.98	0.89	1.08	0.734

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 < 0.000714). Genetic instruments selected from 5 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, MR Mendelian randomization, GWAS genome wide association study, N SNPs number of single-nucleotide polymorphism (genetic instruments), OR odds ratio, CI confidence interval.