Supplementary tables.

Table A: Effect of SNPs on alcohol intake frequency and alcohol drinker status (never vs current). The statistics are derived from linear regression. The GWAS summary data in the table is from UK Biobank. The GWAS identifiers of alcohol intake frequency and alcohol drinker status (never vs current) are corresponding to ukb-b-5779, ukb-a-226 and ukb-d-20117_2 respectively. 1The effect is the mean effect of the increaser allele estimated on a quantile normalized scale. The outlying genetic instruments which had large contribution to Cochran ’s Q statistics are shown in bold. EAF: effect allele frequency; SNP: single nucleotide polymorphism; SE: Standard Error; GWAS: Genome-wide association study. Table B: The effect of the alcohol intake frequency and alcohol drinker status (never vs current) SNPs on self-reported tiredness. The statistics are derived from linear regression. The GWAS summary data in the table is from UK Biobank. The GWAS identifiers of alcohol intake frequency and alcohol drinker status (never vs current) are corresponding to ukb-b-5779, ukb-a-226 and ukb-d-20117_2 respectively. 1The effect is the mean effect of the increaser allele estimated on a quantile normalized scale. EAF: effect allele frequency; SNP: single nucleotide polymorphism; SE: Standard Error; GWAS: Genome-wide association study. Table C: Effect of SNPs on smoking status (never vs current). The statistic are derived from linear regression. The GWAS summary data in the table is from UK Biobank. The GWAS identifiers of smoking status (never vs current) are corresponding to ukb-d-20116_0 and ukb-a-225 respectively. 1The effect is the mean effect of the increaser allele estimated on a quantile normalized scale. The outlying genetic instruments which had large contribution to Cochran ’s Q statistics are shown in bold. EAF: effect allele frequency; SNP: single nucleotide polymorphism; SE: Standard Error; GWAS: Genome-wide association study. Table D: The effect of the smoking status (never vs current) SNPs on self-reported tiredness. 1 The effect is the mean effect of the increaser allele estimated on a quantile normalized scale. EAF: effect allele frequency; SE: Standard Error; SNP: single nucleotide polymorphism; GWAS: Genome-wide association study. Table E: Mendelian Randomization estimates of the causal effect of alcohol intake frequency on self-reported tiredness. Causal effects are estimated using four MR models: inverse variance weighted (IVW), weighted median, penalized median and MR Egger regression. Causal effect estimates are the difference in mean self-reported tiredness (in standard deviation; SD) per 1SD higher alcohol intake frequency. Significant results from Mendelian Randomization analysis are shown in bold. SE: Standard Error; IVs: Instrumental variables. Table F: Mendelian Randomization estimates of the causal effect of alcohol status (current) on self-reported tiredness. Causal effects are estimated using four MR models: inverse variance weighted (IVW), weighted median, penalized median and MR Egger regression. Causal effect estimates are the difference in mean self-reported tiredness (in standard deviation; SD) per 1SD higher alcohol status (current). Table G: Mendelian Randomization estimates of the causal effect of smoking status (never) on self-reported tiredness. Causal effects are estimated using four MR models: inverse variance weighted (IVW), weighted median, penalized median and MR Egger regression. Causal effect estimates are the difference in mean self-reported tiredness (in standard deviation; SD) per 1SD higher alcohol status (never). Significant results from Mendelian Randomization analysis are shown in bold. SE: Standard Error; IVs: Instrumental variables. Table H: Mendelian Randomization estimates of the causal effect of smoking status (current) on self-reported tiredness. Causal effects are estimated using four MR models: inverse variance weighted (IVW), weighted median, penalized median and MR Egger regression. Causal effect estimates are the difference in mean self-reported tiredness (in standard deviation; SD) per 1SD higher alcohol status (current). Table I: Results of heterogeneity tests. Significant results from the heterogeneity tests are shown in bold. Table J: Results of test for directional horizontal pleiotropy. Significant results from the directional horizontal pleiotropy tests are shown in bold. SE: Standard Error. (XLSX)