Table 2 Mendelian randomization results.

From: Genetic overlap and causal associations between smoking behaviours and mental health

Exposure	Outcome	n SNP	MR-IVW results			GSMR results			MR-Egger			Weighted median			Weighted mode
Exposure	Outcome	n SNP	Beta	95% CI	p	Beta	95% CI	p	Beta	95% CI	p	Beta	95% CI	p	Beta	95% CI	p
Smoking and psychiatric disorders
Smoking initiation	Schizophrenia	92	0.665	0.315; 1.016	1.99 × 10^–4	0.579	0.371; 0.788	5.33 × 10^–8	0.305	− 1.523; 2.134	0.744	0.385	0.031; 0.740	0.033	0.067	− 0.992; 1.126	0.901
Schizophrenia	Smoking initiation	125	0.017	0.009;0.024	1.35 × 10^–5	0.015	0.010; 0.020	1.18 × 10^–8	0.047	0.017; 0.078	0.003	0.019	0.010; 0.028	4.82 × 10^–6	0.034	0.003; 0.066	0.036
Smoking initiation^a	Major depression	20	0.434	0.238; 0.630	1.39 × 10^–5	0.365	0.248; 0.482	8.99 × 10^–10	− 0.845	− 2.041; 0.351	0.183	0.324	0.128; 0.519	0.001	0.061	− 0.296; 0.418	0.771
Major depression	Smoking initiation^a	29	− 0.000	− 0.003; 0.003	0.930	− 0.000	− 0.002; 0.002	0.896	0.135	0.047; 0.224	0.006	− 0.001	− 0.004; 0.003	0.642	− 0.003	− 0.010; 0.005	0.449
Smoking initiation	Bipolar disorder	106	0.902	0.520; 1.283	3.61 × 10^–6	0.812	0.515; 1.108	7.82 × 10^–8	0.795	− 1.076; 2.666	0.407	0.800	0.341; 1.259	0.001	0.893	− 0.237; 2.023	0.124
Bipolar disorder	Smoking initiation	18	0.008	− 0.011; 0.027	0.415	0.006	− 0.007; 0.019	0.356	− 0.098	− 0.213; 0.016	0.112	− 0.003	− 0.023; 0.017	0.767	− 0.009	− 0.042; 0.023	0.578
Smoking and positive psychotic experiences in adults
Smoking initiation^a	Auditory hallucinations	21	0.004	− 0.006; 0.014	0.447	0.004	− 0.004; 0.011	0.323	− 0.012	− 0.069; 0.045	0.680	0.001	− 0.010; 0.013	0.813	− 0.004	− 0.023; 0.016	0.709
Auditory hallucinations	Smoking initiation^a	90	− 0.114	− 0.645; 0.418	0.675	− 0.119	− 0.637; 0.398	0.651	0.623	− 0.547; 1.793	0.299	− 0.242	− 0.997; 0.513	0.529	− 0.432	− 2.362; 1.497	0.662
Smoking initiation^a	Visual hallucinations	21	0.001	− 0.009; 0.011	0.859	0.001	− 0.009; 0.011	0.820	− 0.023	− 0.079; 0.033	0.423	− 0.002	− 0.016; 0.012	0.805	− 0.004	− 0.032; 0.025	0.798
Visual hallucinations	Smoking initiation^a	81	0.217	− 0.206; 0.640	0.314	0.197	− 0.212; 0.605	0.345	0.499	− 0.496; 1.495	0.329	0.192	− 0.388; 0.771	0.517	0.175	− 1.187; 1.538	0.802
Smoking initiation^a	Delusions of reference	21	0.003	− 0.002; 0.007	0.276	0.003	− 0.002; 0.007	0.280	0.009	− 0.019; 0.036	0.543	0.001	− 0.005; 0.008	0.669	− 0.005	− 0.020; 0.010	0.545
Delusions of reference	Smoking initiation^a	105	0.003	− 0.725; 0.731	0.994	− 0.042	− 0.801; 0.717	0.914	− 0.449	− 1.951; 1.054	0.560	− 0.234	− 1.316; 0.848	0.672	0.392	− 2.565; 3.349	0.795
Smoking initiation^a	Delusions of persecution	21	0.003	− 0.001; 0.008	0.168	0.003	− 0.002; 0.008	0.193	− 0.003	− 0.031; 0.025	0.820	0.003	− 0.004; 0.009	0.441	0.002	− 0.011; 0.015	0.807
Delusions of persecution	Smoking initiation^a	94	0.154	− 0.657; 0.964	0.710	0.149	− 0.608; 0.907	0.700	− 0.044	− 1.756; 1.670	0.960	− 0.324	− 1.383; 0.736	0.549	− 1.034	− 3.733; 1.664	0.454
Smoking and schizotypy
Smoking initiation	Hypomania	98	0.241	− 0.240; 0.723	0.326	0.235	− 0.224; 0.695	0.316	0.069	− 2.125; 2.264	0.951	0.111	− 0.554; 0.775	0.744	− 0.040	− 1.653; 1.573	0.961
Hypomania	Smoking initiation	68	− 0.001	− 0.006; 0.004	0.644	− 0.001	− 0.005; 0.003	0.565	− 0.004	− 0.014; 0.007	0.494	− 0.002	− 0.008; 0.004	0.455	− 0.003	− 0.015; 0.009	0.609
Smoking initiation	Perceptual aberrations	98	0.065	− 0.438; 0.568	0.800	0.036	− 0.412; 0.490	0.878	0.591	− 1.699; 2.881	0.614	0.154	− 0.502; 0.810	0.645	0.744	− 0.740; 2.227	0.328
Perceptual aberrations	Smoking initiation	54	− 0.001	− 0.005; 0.004	0.731	− 0.000	− 0.005; 0.004	0.867	− 0.001	− 0.011; 0.008	0.792	− 0.001	− 0.008; 0.006	0.729	0.000	− 0.011; 0.010	0.951
Smoking initiation	Physical anhedonia	98	− 0.166	− 0.684; 0.351	0.528	− 0.139	− 0.599; 0.320	0.553	− 0.464	− 2.819; 1.891	0.700	− 0.170	− 0.861; 0.521	0.630	− 0.180	− 1.771; 1.411	0.825
Physical anhedonia	Smoking initiation	58	− 0.001	− 0.006; 0.004	0.678	− 0.000	− 0.005; 0.004	0.850	0.003	− 0.009; 0.015	0.626	0.002	− 0.005; 0.009	0.530	0.010	− 0.006; 0.027	0.222
Smoking initiation	Social anhedonia	98	− 0.454	− 0.935; 0.028	0.065	− 0.414	− 0.870; 0.043	0.076	− 0.579	− 2.770; 1.611	0.605	− 0.469	− 1.131; 0.194	0.166	− 0.326	− 1.963; 1.311	0.697
Social anhedonia	Smoking initiation	57	− 0.001	− 0.005; 0.004	0.746	− 0.001	− 0.005; 0.004	0.754	0.005	− 0.004; 0.014	0.294	0.002	− 0.004; 0.008	0.578	0.004	− 0.008; 0.015	0.523
Smoking and adolescent PENS
Smoking initiation	Paranoia/hallucinations	57	0.338	− 0.076; 0.753	0.110	0.282	− 0.135; 0.700	0.185	0.437	− 1.517; 2.391	0.663	0.073	− 0.518; 0.665	0.808	− 0.056	− 1.188; 1.077	0.923
Paranoia/hallucinations	Smoking initiation	24	− 0.001	− 0.013; 0.011	0.880	− 0.002	− 0.013; 0.009	0.720	− 0.015	− 0.045; 0.015	0.330	− 0.006	− 0.022; 0.010	0.461	− 0.015	− 0.043; 0.014	0.331
Smoking initiation	Cognitive disorganisation	57	1.077	0.576; 1.578	2.55 × 10^–5	1.030	0.518; 1.541	8.02 × 10^–5	2.321	− 0.013; 4.654	0.056	1.267	0.566; 1.969	6.31 × 10^–4	1.352	− 0.101; 2.805	0.074
Cognitive disorganisation	Smoking initiation	28	0.006	− 0.003; 0.015	0.190	0.004	− 0.004; 0.012	0.307	− 0.022	− 0.043; − 0.001	0.059	0.002	− 0.009; 0.013	0.720	− 0.001	− 0.020; 0.019	0.945
Smoking initiation	Anhedonia	57	0.061	− 0.444; 0.568	0.811	0.058	− 0.420; 0.536	0.812	− 0.841	− 3.209; 1.528	0.490	− 0.075	− 0.754; 0.603	0.828	− 0.218	− 1.526; 1.090	0.745
Anhedonia	Smoking initiation	30	− 0.003	− 0.011; 0.006	0.533	− 0.002	− 0.010; 0.006	0.599	− 0.000	− 0.018; 0.018	0.965	− 0.000	− 0.012; 0.011	0.944	0.002	− 0.019; 0.023	0.864
Smoking initiation	Negative symptoms	57	0.523	0.074; 0.973	0.023	0.506	0.105; 0.906	0.013	1.221	− 0.914; 3.356	0.267	0.450	− 0.125; 1.025	0.125	0.529	− 0.492; 1.550	0.315
Negative symptoms	Smoking initiation	25	− 0.002	− 0.014; 0.009	0.712	− 0.003	− 0.014; 0.008	0.609	− 0.012	− 0.042; 0.018	0.436	− 0.004	− 0.019; 0.012	0.656	0.004	− 0.023; 0.031	0.770

GSMR, Generalized Summary-based Mendelian Randomization; MR-IVW, inverse-variance weighted Mendelian randomization; n SNPs, number of variants remaining in analyses after those identified as Heidi-outliers or with residual LD at r² > .1 were removed; PENS, psychotic experiences and negative symptom traits; SNPs identified as having residual LD and as Heidi outliers were also excluded from MR Egger, Weighted Median and Weighted Mode analyses; Bold text indicates significant p values at p < 0.05.
^aSummary statistics for smoking initiation excluded UK Biobank participants in analyses on major depression and adult psychotic experiences to avoid overlapping samples (N = 249,171).

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Table 2 Mendelian randomization results.

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