Supplemental Materials s9

Supplemental Materials Age at First Use and Later Substance Use Disorder: Shared Genetic and Environmental Pathways for Nicotine, Alcohol, and Cannabis by L. S. Richmond-Rakerd et al., 2016, Journal of Abnormal Psychology http://dx.doi.org/10.1037/abn0000191

Table S1. Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Nicotine Dependence

Table S2. Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Alcohol Use Disorder

Table S3. Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Cannabis Use Disorder

Table S4. Univariate Model-Fitting Results for the Age of Substance Use Initiation

Table S5. Independent Pathway Model Estimates of the Proportion of Variation in the Age of Substance Use Initiation Attributable to Common and Substance-Specific Genetic and Environmental Factors

Table S6. Common Pathway Model Estimates of the Proportion of Variation in the Age of Substance Use Initiation Attributable to Common and Substance-Specific Genetic and Environmental Factors

Table S7. Univariate Model-Fitting Results for Substance Use Disorder

Table S8. Independent Pathway Model Estimates of the Proportion of Variation in Substance Use Disorder Attributable to Common and Substance-Specific Genetic and Environmental Factors

Table S9. Common Pathway Model Estimates of the Proportion of Variation in Substance Use Disorder Attributable to Common and Substance-Specific Genetic and Environmental Factors Table S1 Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Nicotine Dependence Log- Model Likelihood Δχ2 df p-value Cohort II Base -10108.38 -- 14 Sex as covariate -10105.71 4.95 15 .0261 Tests of DIF Tolerance -10068.00 75.32 16 <.0001 Withdrawal -10104.62 2.09 16 .1479 Larger/longer -10087.75 35.94 16 <.0001 Cut down/control -10105.64 0.15 16 .7029 Time spent -10105.71 0.00 16 1.000 Role failure -10105.67 0.08 16 .7775 Continued use despite problems -10103.80 3.74 16 .0532 Cohort III Base -4839.78 14 Sex as covariate -4838.21 3.92 15 .0477 Tests of DIF Tolerance -4827.77 17.89 16 <.0001 Withdrawal -4836.39 3.44 16 .0637 Larger/longer -4835.54 4.99 16 .0255 Cut down/control -4838.18 0.07 16 .7884 Time spent -4836.41 3.47 16 .0625 Role failure -4838.18 0.07 16 .7961 Continued use despite problems -4828.78 17.03 16 <.0001

Notes. In the multiple-group confirmatory factor analysis preceding tests of differential item functioning, the loadings and thresholds for the nicotine dependence items could not be equated across men and women in Cohort II or Cohort III (Cohort II: Δχ2=128.94, df=12, p<.0001; Cohort III: Δχ2=52.45, df=12, p<.0001). Nested models were compared using the Satorra- Bentler scaled chi-square difference test. All chi-square difference tests have 1 df. A Bonferroni correction for multiple comparisons was applied at α=.05. Bolded text indicates significant result at p<.007. Table S2 Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Alcohol Use Disorder Log- Model likelihood Δχ2 df p-value Cohort II Base -13167.14 22 Sex as covariate -13020.10 313.51 23 <.0001 Tests of DIF Role failure -13019.73 0.74 24 .3904 Hazardous use -13015.11 10.26 24 .0016 Legal problems -13008.47 21.00 24 <.0001 Social problems -13019.23 1.74 24 .1868 Tolerance -13018.70 2.76 24 .0965 Withdrawal -13019.76 0.69 24 .4055 Larger/longer -13008.53 23.78 24 <.0001 Cut down/control -13020.04 0.12 24 .7253 Time spent -13007.43 24.98 24 <.0001 Reduced activities -12988.30 59.74 24 <.0001 Continued use despite problems -13008.36 23.32 24 <.0001 Cohort III Base -8525.77 22 Sex as covariate -8423.18 208.97 23 <.0001 Tests of DIF Role failure -8421.02 3.88 24 .0488 Hazardous use -8422.32 1.66 24 .1977 Legal problems -8406.80 30.65 24 <.0001 Table S2 continued Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Alcohol Use Disorder Social problems -8421.73 2.86 24 .0907 Tolerance -8420.84 4.56 24 .0327 Withdrawal -8420.74 4.78 24 .0288 Larger/longer -8421.00 4.52 24 .0334 Cut down/control -8422.45 1.43 24 .2314 Time spent -8397.68 50.41 24 <.0001 Reduced activities -8414.12 17.10 24 <.0001 Continued use despite problems -8420.78 4.74 24 .0295 Notes. In the multiple-group confirmatory factor analysis preceding tests of differential item functioning, the loadings and thresholds for the alcohol use disorder items could not be equated across men and women in Cohort II or Cohort III (Cohort II: Δχ2=188.92, df=20, p<.0001; Cohort III: Δχ2=131.82, df=20, p<.0001). Nested models were compared using the Satorra- Bentler scaled chi-square difference test. All chi-square difference tests have 1 df. A Bonferroni correction for multiple comparisons was applied at α=.05. Bolded text indicates significant result at p<.005. Table S3 Results of Multiple Indicator Multiple Causes (MIMIC) Model Analyses for Cannabis Use Disorder Log- Model likelihood Δχ2 df p-value Cohort II Base -5399.26 12 Sex as covariate -5380.46 37.39 13 <.0001 Tests of DIF Larger/longer -5378.92 3.00 14 .0830 Tolerance -5380.11 0.70 14 .4021 Hazardous use -5372.64 15.76 14 .0001 Role interference -5380.45 0.03 14 .8647 Continued use despite problems -5378.55 3.73 14 .0533 Cut down/control -5380.24 0.44 14 .5062 Cohort III Base -2763.23 12 Sex as covariate -2746.21 34.03 13 <.0001 Tests of DIF Larger/longer -2740.39 11.64 14 .0008 Tolerance -2745.76 0.89 14 .3476 Hazardous use -2737.76 16.91 14 <.0001 Role interference -2746.16 0.11 14 .7489 Continued use despite problems -2745.91 0.60 14 .4438 Cut down/control -2744.84 2.73 14 .1027

Notes. In the multiple-group confirmatory factor analysis preceding tests of differential item functioning, the loadings and thresholds for the cannabis use disorder items could not be equated across men and women in Cohort II or Cohort III (Cohort II: Δχ2=25.93, df=10, p=.004; Cohort III: Δχ2=27.19, df=10, p=.002). Nested models were compared using the Satorra-Bentler scaled chi-square difference test. All chi-square difference tests have 1 df. A Bonferroni correction for multiple comparisons was applied at α=.05. Bolded text indicates significant result at p<.008.

Table S4 Univariate Model-Fitting Results for the Age of Substance Use Initiation Δχ2 df p-value AIC Tobacco I. ACE model -- 12 -- 33510.63 II. AE model 7.60 14 .0223 33518.97 III. CE model 12.02 14 .0024 33527.53 IV. Model I with A equated across sex 0.54 13 .4626 33509.54 V. Model I with C equated across sex 0.02 13 .8818 33508.66 VI. Model I with A and C equated across sex 6.35 14 .0418 33523.20 VII. Model I with E equated across sex 7.99 13 .0047 33523.98 Alcohol I. ACE model -- 12 -- 32940.89 II. AE model 6.19 14 .0452 32950.41 III. CE model 7.44 14 .0243 32953.67 IV. Model I with A, C, and E equated across sex 0.36 15 .9482 32935.89 Cannabis I. ACE model -- 12 -- 23165.10 II. AE model 13.67 14 .0011 23181.06 III. CE model 4.05 14 .1318 23168.19 IV. Model I with A equated across sex 0.01 13 .9258 23163.11 V. Model I with C equated across sex 0.09 13 .7594 23163.24 VI. Model I with E equated across sex 3.12 13 .0772 23169.47 VII. Model I with A, C, and E equated across sex 9.78 15 .0205 23175.51

Notes. Nested models were compared using the Satorra-Bentler scaled chi-square difference test. A=additive genetic, C=shared environment, E=unique environment. Table S5 Independent Pathway Model Estimates of the Proportion of Variation in the Age of Substance Use Initiation Attributable to Common and Substance-Specific Genetic and Environmental Factors Shared Unique Additive Genetic Environment Environment Tota Substance CF Sp l CF Sp Total CF Sp Total Men Tobacco .04 .16 .20 .19 .00 .19 .13 .48 .61 Alcohol .11 .18 .29 .09 .06 .15 .18 .37 .55 Cannabis .19 .05 .24 .04 .29 .33 .05 .40 .45 Women Tobacco .03 .30 .33 .17 .04 .21 .10 .36 .46 Alcohol .23 .00 .23 .07 .14 .21 .06 .50 .56 Cannabis .05 .18 .23 .28 .01 .29 .06 .41 .47

Notes. Variance estimates do not always sum exactly to 1.00 due to rounding. CF=common factor, Sp=specific factor. Table S6 Common Pathway Model Estimates of the Proportion of Variation in the Age of Substance Use Initiation Attributable to Common and Substance-Specific Genetic and Environmental Factors Additive Genetic Shared Environment Unique Environment Phenotype CF Sp Total CF Sp Total CF Sp Total Men Common Factor .32 -- .32 .30 -- .30 .38 -- .38 Tobacco .10 .16 .26 .09 .05 .14 .11 .48 .59 Alcohol .13 .17 .30 .12 .03 .16 .15 .39 .55 Cannabis .07 .14 .21 .06 .27 .33 .08 .37 .45 Women Common Factor .20 -- .20 .55 -- .55 .25 -- .25 Tobacco .05 .28 .34 .15 .05 .20 .07 .39 .46 Alcohol .05 .16 .21 .14 .10 .23 .06 .50 .56 Cannabis .08 .17 .25 .21 .06 .27 .10 .38 .48

Notes. Variance estimates do not always sum exactly to 1.00 due to rounding. CF=common factor, Sp=specific factor. Table S7 Univariate Model-Fitting Results for Substance Use Disorder Δχ2 df p-value AIC Tobacco 26102.4 I. ACE model -- 12 -- 4 26098.7 II. AE model .43 14 .81 4 26196.7 III. CE model 107.54 14 <.0001 3 26097.0 IV. Model I with A, C, and E equated across sex 0.82 15 .8435 9 Alcohol 13289.4 I. ACE model -- 12 -- 9 13289.9 II. AE model 2.62 14 .2704 7 13334.0 III. CE model 86.89 14 <.0001 6 13288.3 IV. Model I with A equated across sex 0.74 13 .3902 3 13288.9 V. Model I with C equated across sex 1.41 13 .2366 7 13290.2 VI. Model I with E equated across sex 2.32 13 .1274 1 13347.2 VII. Model I with A, C, and E equated across sex 109.00 15 <.0001a 9 Cannabis I. ACE model -- 12 -- 8161.02 II. AE model 1.99 14 .3689 8159.84 III. CE model 12.94 14 .0016 8177.66 IV. Model I with A equated across sex 2.31 13 .1284 8162.51 V. Model I with C equated across sex 0.12 13 .7331 8159.19 VI. Model I with E equated across sex 0.33 13 .5679 8159.61 VII. Model I with A, C, and E equated across sex 30.53 15 <.0001 8199.76

Notes. a The standardized estimates of A, C, and E were very similar in men and women, suggesting that variance differences may be the major source of a sex effect. Nested models were compared using the Satorra-Bentler scaled chi-square difference test. A=additive genetic, C=shared environment, E=unique environment. Table S8 Independent Pathway Model Estimates of the Proportion of Variation in Substance Use Disorder Attributable to Common and Substance-Specific Genetic and Environmental Factors Shared Unique Additive Genetic Environment Environment Tota Substance CF Sp l CF Sp Total CF Sp Total Men Tobacco .26 .31 .57 .03 .00 .03 .02 .38 .40 Alcohol .34 .04 .38 .01 .10 .11 .14 .37 .51 Cannabis .25 .17 .42 .11 .00 .11 .04 .43 .47 Women Tobacco .28 .23 .51 .07 .00 .07 .05 .38 .43 Alcohol .17 .21 .38 .02 .00 .02 .06 .54 .60 Cannabis .07 .19 .26 .17 .00 .17 .21 .37 .58

Notes. Variance estimates do not always sum exactly to 1.00 due to rounding. CF=common factor, Sp=specific factor. Table S9 Common Pathway Model Estimates of the Proportion of Variation in Substance Use Disorder Attributable to Common and Substance-Specific Genetic and Environmental Factors Additive Genetic Shared Environment Unique Environment Phenotype CF Sp Total CF Sp Total CF Sp Total Men Common Factor .86 -- .86 .00 -- .00 .14 -- .14 Tobacco .29 .31 .60 .00 .00 .00 .05 .35 .40 Alcohol .29 .06 .35 .00 .14 .14 .05 .46 .51 Cannabis .29 .13 .43 .00 .10 .10 .05 .43 .47 Women Common Factor .55 -- .55 .19 -- .19 .25 -- .25 Tobacco .21 .28 .49 .07 .00 .07 .10 .33 .43 Alcohol .14 .20 .34 .05 .00 .05 .06 .54 .61 Cannabis .17 .12 .29 .06 .09 .15 .08 .49 .57

Notes. Variance estimates do not always sum exactly to 1.00 due to rounding. CF=common factor, Sp=specific factor.