Supplementary Material for the Article:


Adolescent cannabis use and adult psychoticism:

A longitudinal co-twin control analysis using data from two cohorts


Jonathan D. Schaefer, Ph.D.,1 Seon-kyeong Jang, M.A.,2 Scott Vrieze, Ph.D.,2

William G. Iacono, Ph.D.,2 Matt McGue, Ph.D.,2 & Sylia Wilson, Ph.D.1


1Institute for Child Development, University of Minnesota, Minneapolis, MN, USA

2Department of Psychology, University of Minnesota, Minneapolis, MN, USA


This material supplements, but does not replace, the peer-reviewed paper in

The Journal of Abnormal Psychology.


Correspondence:

Jonathan D. Schaefer, Ph.D
Institute of Child Development, University of Minnesota
51 E. River Rd., Minneapolis, MN 55455
schae567@umn.edu







Supplemental Table 1. Results from individual-level models predicting adult psychoticism as a function of the cannabis use index as well as mean scores on its constituent items (i.e., frequency of cannabis use, number of uses).

 

Individual-level models


Exposure

Psychoticism Scale

N

Estimate (95% CI)

p value

Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

1544

0.14 (0.09, 0.19)

<0.001

Unusual Beliefs & Experiences

0.12 (0.07, 0.17)

<0.001

Eccentricity

0.10 (0.05, 0.15)

<0.001

Perceptual Dysregulation

0.16 (0.11, 0.21)

<0.001

Frequency of Cannabis Use

PID-5 Psychoticism

1544

0.13 (0.08, 0.18)

<0.001

Unusual Beliefs & Experiences

0.11 (0.06, 0.16)

<0.001

Eccentricity

0.10 (0.05, 0.15)

<0.001

Perceptual Dysregulation

0.14 (0.09, 0.19)

<0.001

Number of Uses

PID-5 Psychoticism

1544

0.13 (0.08, 0.19)

<0.001

Unusual Beliefs & Experiences

0.12 (0.07, 0.17)

<0.001

Eccentricity

0.10 (0.05, 0.15)

<0.001

Perceptual Dysregulation

0.15 (0.10, 0.20)

<0.001


Notes. Individual-level analyses examined associations between cumulative adolescent cannabis use index or mean scores on constituent items and young adult scores on the PID-5 Psychoticism factor or its facets. Estimates are reported as standardized betas, reflecting the standard deviation increase in Psychoticism associated with each standard deviation increase in each measure of cumulative cannabis use. The number of complete pairs contributing data to each set of analyses is 679 for the cannabis use index and 644 for cannabis use disorder. The number of families contributing data to each set of analyses is 865 for the cannabis use index and 814 for cannabis use disorder. All models included participant age, sex, zygosity, and cohort as covariates. CI = confidence interval.







Supplemental Table 2. Results from co-twin control models predicting adult psychoticism as a function of the cannabis use index as well as mean scores on its constituent items (i.e., frequency of cannabis use, number of uses).

 


 

Co-twin control models


 


Between-pair effect

 

Within-pair effect

Exposure

Psychoticism Scale

N

 

Estimate (95% CI)

p value

 

Estimate (95% CI)

p value

Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

1544


0.18 (0.12, 0.24)

<0.001


0.00 (-0.10, 0.10)

0.965

Unusual Beliefs & Experiences


0.16 (0.11, 0.22)

<0.001


-0.01 (-0.12, 0.09)

0.840

Eccentricity


0.14 (0.08, 0.20)

<0.001


0.00 (-0.09, 0.10)

0.930

Perceptual Dysregulation


0.20 (0.14, 0.26)

<0.001


0.01 (-0.09, 0.12)

0.805

Frequency of Cannabis Use

PID-5 Psychoticism

1544


0.19 (0.13, 0.25)

<0.001


-0.02 (-0.11, 0.07)

0.598

Unusual Beliefs & Experiences


0.17 (0.11, 0.23)

<0.001


-0.04 (-0.14, 0.05)

0.380

Eccentricity


0.15 (0.09, 0.21)

<0.001


-0.01 (-0.10, 0.08)

0.813

Perceptual Dysregulation


0.21 (0.15, 0.26)

<0.001


-0.01 (-0.11, 0.08)

0.779

Number of Uses

PID-5 Psychoticism

1544


0.17 (0.11, 0.23)

<0.001


0.02 (-0.08, 0.12)

0.696

Unusual Beliefs & Experiences


0.15 (0.10, 0.21)

<0.001


0.02 (-0.09, 0.12)

0.750

Eccentricity


0.13 (0.07, 0.19)

<0.001


0.02 (-0.08, 0.12)

0.691

Perceptual Dysregulation


0.19 (0.13, 0.25)

<0.001


0.01 (-0.09, 0.12)

0.810


Notes. Co-twin control analyses decompose effects from individual-level models into between-pair (reflecting pre-existing, shared familial liability) and within-pair (cannabis exposure) effects. Estimates are reported as standardized betas, reflecting the standard deviation increase in Psychoticism associated either with each standard deviation increase in each measure of cumulative cannabis use. Because standardization was conducted at the phenotypic level, betas for the within-pair effects of the adolescent cannabis use index should be interpreted in terms of the SD for the entire sample rather than the SD of twin differences. The number of complete pairs contributing data to each set of analyses is 679 for the cannabis use index and 644 for cannabis use disorder. The number of families contributing data to each set of analyses is 865 for the cannabis use index and 814 for cannabis use disorder. All models included participant age, sex, zygosity, and cohort as covariates. CI = confidence interval.



Supplemental Table 3. Full results from individual-level models testing for associations between adolescent cannabis exposure and adult psychoticism.


  1. Cumulative Adolescent Cannabis Use Index



Outcome

Predictors

N


Psychoticism

Unusual Beliefs & Experiences

Eccentricity

Perceptual Dysregulation

Cannabis Use Index



0.14***

0.12***

0.10***

0.16***



( 0.09, 0.19)

( 0.07, 0.17)

( 0.05, 0.15)

( 0.11, 0.21)

Sex (ref: female)



0.39***

0.34***

0.40***

0.23***



( 0.26, 0.51)

( 0.22, 0.46)

( 0.28, 0.53)

( 0.11, 0.36)

Zygosity (ref: DZ)

1544


-0.04

-0.01

-0.04

-0.04



(-0.15, 0.08)

(-0.12, 0.10)

(-0.15, 0.07)

(-0.15, 0.07)

Age



-0.35*

-0.18

-0.37*

-0.36*



(-0.63, -0.07)

(-0.46, 0.10)

(-0.65, -0.09)

(-0.64, -0.08)

Cohort (ref: Cohort 2)



-0.28

-0.11

-0.31

-0.31



(-0.85, 0.28)

(-0.67, 0.45)

(-0.88, 0.25)

(-0.87, 0.25)


  1. Adolescent Cannabis Use Disorder



Outcome

Predictors

N


Psychoticism

Unusual Beliefs & Experiences

Eccentricity

Perceptual Dysregulation

Cannabis Use Disorder (ref: absent)



0.35***

0.31***

0.29***

0.36***



( 0.20, 0.50)

( 0.16, 0.47)

( 0.14, 0.44)

( 0.21, 0.52)

Sex (ref: female)



0.40***

0.35***

0.41***

0.26***



( 0.27, 0.53)

( 0.22, 0.48)

( 0.28, 0.54)

( 0.13, 0.38)

Zygosity (ref: DZ)

1458


-0.03

0.01

-0.03

-0.05



(-0.14, 0.09)

(-0.11, 0.12)

(-0.15, 0.08)

(-0.16, 0.07)

Age



-0.37*

-0.21

-0.38*

-0.39**



(-0.67, -0.08)

(-0.50, 0.08)

(-0.68, -0.09)

(-0.68, -0.09)

Cohort (ref: Cohort 2)



-0.31

-0.15

-0.32

-0.35



(-0.90, 0.27)

(-0.73, 0.43)

(-0.91, 0.26)

(-0.93, 0.23)


Notes. Individual-level analyses examined associations between (A) cumulative adolescent cannabis use index or (B) adolescent cannabis use disorder diagnosis and young adult scores on the PID-5 Psychoticism factor and its facets. Estimates for continuous predictors are reported as standardized betas with 95% confidence intervals, reflecting the standard deviation increase in each outcome associated with a standard deviation increase in each predictor. Estimates for binary predictors are standardized betas with 95% confidence intervals reflecting the difference in each outcome associated with scoring a “1” on this variable (vs. “0” for the reference category). The number of complete pairs contributing data to each set of analyses is 679 for the cannabis use index and 644 for cannabis use disorder. The number of families contributing data to each set of analyses is 865 for the cannabis use index and 814 for cannabis use disorder. *p<0.05, **p<0.01, ***p<0.001

Supplemental Table 4. Results from cohort-specific individual-level models of adolescent cannabis exposure and adult psychoticism.


 

Combined sample


Cohort 1


Cohort 2

Exposure

Psychoticism Scale

N

Estimate (95% CI)

p value

 

N

Estimate (95% CI)

p value


N

Estimate (95% CI)

p value

Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

1544

0.14 (0.09, 0.19)

<0.001


724

0.16 (0.08, 0.24)

<0.001


820

0.12 (0.06, 0.18)

<0.001

Unusual Beliefs & Experiences

0.12 (0.07, 0.17)

<0.001


0.14 (0.06, 0.22)

<0.001


0.11 (0.04, 0.17)

0.001

Eccentricity

0.10 (0.05, 0.15)

<0.001


0.12 (0.04, 0.21)

0.004


0.09 (0.03, 0.15)

0.006

Perceptual Dysregulation

0.16 (0.11, 0.21)

<0.001


0.19 (0.10, 0.27)

<0.001


0.13 (0.07, 0.19)

<0.001

Adolescent Cannabis Use Disorder

PID-5 Psychoticism

1458

0.35 (0.20, 0.50)

<0.001


688

0.60 (0.35, 0.84)

<0.001


770

0.13 (-0.05, 0.31)

0.160

Unusual Beliefs & Experiences

0.31 (0.16, 0.47)

<0.001


0.57 (0.33, 0.81)

<0.001


0.09 (-0.11, 0.28)

0.379

Eccentricity

0.29 (0.14, 0.44)

<0.001


0.48 (0.24, 0.73)

<0.001


0.13 (-0.06, 0.31)

0.178

Perceptual Dysregulation

0.36 (0.21, 0.52)

<0.001


0.60 (0.34, 0.85)

<0.001


0.17 (-0.01, 0.35)

0.067


Note: Individual-level analyses examined associations between cumulative adolescent cannabis use index or adolescent cannabis use disorder diagnosis and young adult scores on the PID-5 Psychoticism factor and its facets. Estimates are reported as standardized betas, reflecting the standard deviation increase in Psychoticism associated either (a) with each standard deviation increase in cumulative adolescent cannabis use or (b) with an adolescent cannabis use disorder diagnosis (vs. not receiving this diagnosis). The number of complete pairs contributing data to each set of analyses is 679 for the cannabis use index and 644 for cannabis use disorder. The number of families contributing data to each set of analyses is 865 for the cannabis use index and 814 for cannabis use disorder. All models included participant age, sex, zygosity, and cohort as covariates. CI = confidence interval.



Supplemental Table 5. Cohort-specific co-twin control models of adolescent cannabis exposure and adult psychoticism.


A. Full Analytic Sample

 


Between-pair effect

 

Within-pair effect

Exposure

Psychoticism Scale

N

Estimate (95% CI)

p value

 

Estimate (95% CI)

p value


Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

1544

0.18 (0.12, 0.24)

<0.001


0.00 (-0.10, 0.10)

0.965


Unusual Beliefs & Experiences

0.16 (0.11, 0.22)

<0.001


-0.01 (-0.12, 0.09)

0.840


Eccentricity

0.14 (0.08, 0.20)

<0.001


0.00 (-0.09, 0.10)

0.930


Perceptual Dysregulation

0.20 (0.14, 0.26)

<0.001


0.01 (-0.09, 0.12)

0.805


Adolescent Cannabis Use Disorder

PID-5 Psychoticism

1458

0.55 (0.36, 0.74)

<0.001


0.02 (-0.22, 0.26)

0.865


Unusual Beliefs & Experiences

0.48 (0.29, 0.67)

<0.001


0.00 (-0.27, 0.26)

0.980


Eccentricity

0.43 (0.24, 0.62)

<0.001


0.06 (-0.18, 0.31)

0.607


Perceptual Dysregulation

0.59 (0.40, 0.78)

<0.001


-0.04 (-0.29, 0.22)

0.784



B. Cohort 1

 


Between-pair effect

 

Within-pair effect

Exposure

Psychoticism Scale

N

 

Estimate (95% CI)

p value

 

Estimate (95% CI)

p value

Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

724


0.20 (0.11, 0.30)

<0.001


0.00 (-0.19, 0.18)

0.960

Unusual Beliefs & Experiences


0.17 (0.08, 0.26)

<0.001


0.01 (-0.19, 0.20)

0.936

Eccentricity


0.16 (0.06, 0.25)

0.001


-0.01 (-0.20, 0.17)

0.890

Perceptual Dysregulation


0.23 (0.14, 0.33)

<0.001


0.00 (-0.19, 0.19)

0.988

Adolescent Cannabis Use Disorder

PID-5 Psychoticism

688


0.78 (0.49, 1.08)

<0.001


0.22 (-0.21, 0.64)

0.318

Unusual Beliefs & Experiences


0.66 (0.38, 0.95)

<0.001


0.32 (-0.14, 0.78)

0.170

Eccentricity


0.61 (0.32, 0.91)

<0.001


0.21 (-0.22, 0.64)

0.335

Perceptual Dysregulation


0.86 (0.56, 1.16)

<0.001


0.00 (-0.45, 0.45)

0.995





C. Cohort 2

 


Between-pair effect

 

Within-pair effect

Exposure

Psychoticism Scale

N

 

Estimate (95% CI)

p value

 

Estimate (95% CI)

p value

Cumulative Adolescent Cannabis Use Index

PID-5 Psychoticism

820


0.16 (0.09, 0.24)

<0.001


0.00 (-0.11, 0.12)

0.939

Unusual Beliefs & Experiences


0.16 (0.08, 0.23)

<0.001


-0.02 (-0.14, 0.10)

0.719

Eccentricity


0.12 (0.05, 0.19)

0.002


0.01 (-0.10, 0.13)

0.823

Perceptual Dysregulation


0.18 (0.11, 0.24)

<0.001


0.02 (-0.09, 0.13)

0.730

Adolescent Cannabis Use Disorder

PID-5 Psychoticism

770


0.32 (0.08, 0.56)

0.010


-0.11 (-0.39, 0.16)

0.432

Unusual Beliefs & Experiences


0.30 (0.05, 0.55)

0.020


-0.22 (-0.52, 0.08)

0.150

Eccentricity


0.24 (0.00, 0.49)

0.050


-0.03 (-0.32, 0.25)

0.827

Perceptual Dysregulation


0.33 (0.10, 0.56)

0.006


-0.06 (-0.34, 0.22)

0.662


Note: Co-twin control analyses decompose effects from individual-level models into between-pair (reflecting pre-existing, shared familial liability) and within-pair (cannabis exposure) effects. Because standardization was conducted at the phenotypic level, betas for the within-pair effects of the adolescent cannabis use index should be interpreted in terms of the SD for the entire sample rather than the SD of twin differences. All models included participant age, sex, zygosity, and cohort as covariates. CI = confidence interval.



Supplemental Table 6. Full results from co-twin control models testing for associations between adolescent cannabis exposure and adult psychoticism.


  1. Cumulative Adolescent Cannabis Use Index



Outcome

Predictors

N


Psychoticism

Unusual Beliefs & Experiences

Eccentricity

Perceptual Dysregulation

Between-Pair Effect

1544


0.18***

0.16***

0.14***

0.20***


( 0.12, 0.24)

( 0.11, 0.22)

( 0.08, 0.20)

( 0.14, 0.26)

Within-Pair Effect


0.00

-0.01

0.00

0.01


(-0.10, 0.10)

(-0.12, 0.09)

(-0.09, 0.10)

(-0.09, 0.12)

Sex (ref: female)


0.38***

0.33***

0.40***

0.23***


( 0.25, 0.50)

( 0.21, 0.46)

( 0.27, 0.52)

( 0.10, 0.35)

Zygosity (ref: DZ)


-0.03

-0.01

-0.03

-0.03


(-0.14, 0.08)

(-0.12, 0.10)

(-0.15, 0.08)

(-0.14, 0.08)

Age


-0.35*

-0.18

-0.37**

-0.36*


(-0.64, -0.07)

(-0.46, 0.10)

(-0.66, -0.09)

(-0.64, -0.08)

Cohort (ref: Cohort 2)


-0.29

-0.11

-0.32

-0.31


(-0.85, 0.27)

(-0.67, 0.45)

(-0.88, 0.25)

(-0.87, 0.25)


  1. Adolescent Cannabis Use Disorder



Outcome

Predictors

N


Psychoticism

Unusual Beliefs & Experiences

Eccentricity

Perceptual Dysregulation

Between-Pair Effect

1458


0.55***

0.48***

0.43***

0.59***


( 0.36, 0.74)

( 0.29, 0.67)

( 0.24, 0.62)

( 0.40, 0.78)

Within-Pair Effect


0.02

-0.00

0.06

-0.04


(-0.22, 0.26)

(-0.27, 0.26)

(-0.18, 0.31)

(-0.29, 0.22)

Sex (ref: female)


0.39***

0.34***

0.40***

0.24***


( 0.26, 0.51)

( 0.21, 0.47)

( 0.27, 0.53)

( 0.11, 0.37)

Zygosity (ref: DZ)


-0.02

0.01

-0.03

-0.04


(-0.13, 0.09)

(-0.10, 0.13)

(-0.14, 0.09)

(-0.15, 0.08)

Age


-0.39**

-0.22

-0.40**

-0.41**


(-0.68, -0.10)

(-0.51, 0.07)

(-0.69, -0.10)

(-0.70, -0.11)

Cohort (ref: Cohort 2)


-0.34

-0.17

-0.34

-0.39


(-0.93, 0.24)

(-0.75, 0.41)

(-0.93, 0.24)

(-0.97, 0.20)


Notes. Co-twin control analyses decompose effects from individual-level models into between-pair (reflecting pre-existing, shared familial liability) and within-pair (cannabis exposure) effects. Estimates for continuous predictors are reported as standardized betas with 95% confidence intervals, reflecting the standard deviation increase in each outcome associated with a standard deviation increase in each predictor. Estimates for binary predictors are standardized betas with 95% confidence intervals reflecting the difference in each outcome associated with scoring a “1” on this variable (vs. “0” for the reference category). Because standardization was conducted at the phenotypic level, betas for the within-pair effects of the adolescent cannabis use index should be interpreted in terms of the SD for the entire sample rather than the SD of twin differences. The number of complete pairs contributing data to each set of analyses is 679 for the cannabis use index and 644 for cannabis use disorder. The number of families contributing data to each set of analyses is 865 for the cannabis use index and 814 for cannabis use disorder. *p<0.05, **p<0.01, ***p<0.001



Supplemental Table 7. Results from discordant twin analyses involving only pairs in which one twin scored ≥2 on our cannabis use index for at least one wave and the other twin reported complete cannabis abstinence.


Psychoticism Scale

N


Estimate (95% CI)

p value

PID-5 Psychoticism

82


0.06 (-0.29, 0.40)

0.750

Unusual Beliefs & Experiences


-0.09 (-0.42, 0.24)

0.593

Eccentricity


0.13 (-0.23, 0.49)

0.470

Perceptual Dysregulation


0.07 (-0.26, 0.41)

0.660


Note: Estimates from discordant twin analyses reflect the standardized mean difference in Psychoticism scores between twins with at least one period of at least moderate adolescent cannabis use (score of ≥ 2 on our cannabis use index at any wave) and co-twins who reported no adolescent cannabis use. All models included participant age, sex, zygosity, and cohort as covariates. CI = confidence interval.



Supplemental Table 8. Full model results from tests for incremental and interaction effects between adolescent cannabis exposure and polygenic risk of schizophrenia in predicting adult psychoticism.


A. Psychoticism

Predictors

Psychoticism

1

2

3


SCHZ-PGS

0.08**

0.07*

0.17


(0.03, 0.14)

(0.02, 0.13)

(-0.09, 0.43)


Cannabis Use Index

-

0.12***

0.10


(0.07, 0.18)

(-0.17, 0.36)


SCHZ-PGS * Cannabis Use Index

-

-

0.01


(-0.05, 0.07)


PC1

0.00

-0.01

0.02


(-0.06, 0.05)

(-0.06, 0.05)

(-0.05, 0.09)


PC2

0.01

0.01

0.01


(-0.04, 0.07)

(-0.05, 0.07)

(-0.05, 0.07)


PC3

0.03

0.04

0.02


(-0.03, 0.09)

(-0.02, 0.10)

(-0.04, 0.08)


PC4

-0.03

-0.04

-0.06*


(-0.09, 0.02)

(-0.02, 0.10)

(-0.12, -0.00)


PC5

0.05

0.04

0.04


(-0.01, 0.10)

(-0.02, 0.10)

(-0.02, 0.11)


PC6

-0.02

-0.02

0.00


(-0.08, 0.04)

(-0.07, 0.04)

(-0.06, 0.06)


PC7

-0.04

-0.04

-0.03


(-0.10, 0.01)

(-0.10, 0.02)

(-0.09, 0.03)


PC8

-0.03

-0.03

-0.03


(-0.09, 0.03)

(-0.08, 0.03)

(-0.09, 0.03)


PC9

0.02

0.02

0.01


(-0.04, 0.08)

(-0.08, 0.04)

(-0.06, 0.07)


PC10

-0.02

-0.02

-0.03


(-0.08, 0.04)

(-0.08, 0.04)

(-0.09, 0.04)


Sex (ref: female)

0.37***

0.36***

0.33***


(0.24, 0.51)

(0.23, 0.49)

( 0.20, 0.47)


Cohort (ref: Cohort 2)

-0.27

-0.33

-0.28


(-0.88, 0.34)

(-0.93, 0.28)

(-0.88, 0.32)


Age

-0.34*

-0.38*

-0.35*


(-0.64, -0.04)

(-0.68, -0.08)

(-0.65, -0.05)


Zygosity (ref: DZ)

-0.06

-0.05

-0.04


(-0.18, 0.06)

(-0.17, 0.06)

(-0.16, 0.08)


SCHZ-PGS * PC1

-

-

-0.05


(-0.10, 0.00)


SCHZ-PGS * PC2

-

-

0.01


(-0.04, 0.07)


SCHZ-PGS * PC3

-

-

-0.03


(-0.09, 0.02)


SCHZ-PGS * PC4

-

-

0.01


(-0.05, 0.07)


SCHZ-PGS * PC5

-

-

-0.02


(-0.08, 0.04)


SCHZ-PGS * PC6

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * PC7

-

-

-0.02


(-0.08, 0.04)


SCHZ-PGS * PC8

-

-

0.04


(-0.02, 0.10)


SCHZ-PGS * PC9

-

-

0.03


(-0.04, 0.10)


SCHZ-PGS * PC10

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * Sex

-

-

0.01


(-0.12, 0.14)


SCHZ-PGS * Cohort

-

-

-0.27


(-0.87, 0.33)


SCHZ-PGS * Age

-

-

-0.08


(-0.38, 0.23)


SCHZ-PGS * Zygosity

-

-

0.04


(-0.07, 0.16)


Cannabis Use Index * PC1

-

-

0.10***


( 0.04, 0.15)


Cannabis Use Index * PC2

-

-

-0.06*


(-0.12, -0.01)


Cannabis Use Index * PC3

-

-

-0.04


(-0.10, 0.02)


Cannabis Use Index * PC4

-

-

0.01


(-0.06, 0.07)


Cannabis Use Index * PC5

-

-

0.01


(-0.05, 0.07)


Cannabis Use Index * PC6

-

-

0.08**


( 0.02, 0.14)


Cannabis Use Index * PC7

-

-

0.02


(-0.04, 0.09)


Cannabis Use Index * PC8

-

-

-0.04


(-0.11, 0.03)


Cannabis Use Index * PC9

-

-

-0.05


(-0.12, 0.03)


Cannabis Use Index * PC10

-

-

0.01


(-0.07, 0.08)


Cannabis Use Index * Sex

-

-

-0.06


(-0.18, 0.07)


Cannabis Use Index * Cohort

-

-

0.05


(-0.51, 0.60)


Cannabis Use Index * Age

-

-

0.01


(-0.26, 0.29)


Cannabis Use Index * Zygosity

-

-

0.04


(-0.07, 0.15)









Predictors

PID-5 Psychoticism

1

2

3


SCHZ-PGS

0.08**

0.08*

0.17


(0.03, 0.14)

(0.02, 0.13)

(-0.10, 0.44)


Cannabis Use Disorder

-

0.28***

0.01


(0.12, 0.43)

(-0.78, 0.79)


SCHZ-PGS * Cannabis Use Disorder

-

-

0.10


(-0.06, 0.26)


PC1

0.00

-0.01

-0.02


(-0.06, 0.05)

(-0.07, 0.04)

(-0.09, 0.06)


PC2

0.01

0.01

0.02


(-0.04, 0.07)

(-0.05, 0.07)

(-0.04, 0.08)


PC3

0.03

0.04

0.04


(-0.03, 0.09)

(-0.02, 0.10)

(-0.02, 0.11)


PC4

-0.03

-0.05

-0.08*


(-0.09, 0.02)

(-0.10, 0.01)

(-0.14, -0.01)


PC5

0.05

0.04

0.04


(-0.01, 0.10)

(-0.02, 0.10)

(-0.03, 0.11)


PC6

-0.02

-0.02

-0.03


(-0.08, 0.04)

(-0.07, 0.04)

(-0.09, 0.03)


PC7

-0.04

-0.04

-0.04


(-0.10, 0.01)

(-0.10, 0.02)

(-0.10, 0.02)


PC8

-0.03

-0.03

-0.02


(-0.09, 0.03)

(-0.08, 0.03)

(-0.08, 0.05)


PC9

0.02

0.02

0.02


(-0.04, 0.08)

(-0.04, 0.08)

(-0.04, 0.09)


PC10

-0.02

-0.02

-0.03


(-0.08, 0.04)

(-0.08, 0.04)

(-0.09, 0.03)


Sex (ref: female)

0.37***

0.36***

0.33***


(0.24, 0.51)

( 0.22, 0.49)

( 0.19, 0.47)


Cohort (ref: Cohort 2)

-0.27

-0.22

-0.19


(-0.88, 0.34)

(-0.83, 0.39)

(-0.84, 0.46)


Age

-0.34*

-0.33*

-0.29


(-0.64, -0.04)

(-0.63, -0.02)

(-0.62, 0.04)


Zygosity (ref: DZ)

-0.06

-0.04

-0.05


(-0.18, 0.06)

(-0.16, 0.08)

(-0.18, 0.08)


SCHZ-PGS * PC1

-

-

-0.05


(-0.10, 0.01)


SCHZ-PGS * PC2

-

-

-0.00


(-0.06, 0.06)


SCHZ-PGS * PC3

-

-

-0.03


(-0.08, 0.03)


SCHZ-PGS * PC4

-

-

0.02


(-0.05, 0.08)


SCHZ-PGS * PC5

-

-

-0.00


(-0.06, 0.06)


SCHZ-PGS * PC6

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * PC7

-

-

-0.02


(-0.07, 0.04)


SCHZ-PGS * PC8

-

-

0.04


(-0.03, 0.10)


SCHZ-PGS * PC9

-

-

0.03


(-0.04, 0.10)


SCHZ-PGS * PC10

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * Sex

-

-

0.02


(-0.11, 0.16)


SCHZ-PGS * Cohort

-

-

-0.30


(-0.92, 0.31)


SCHZ-PGS * Age

-

-

-0.10


(-0.40, 0.21)


SCHZ-PGS * Zygosity

-

-

0.05


(-0.07, 0.17)


Cannabis Use Disorder * PC1

-

-

0.18*


( 0.03, 0.34)


Cannabis Use Disorder * PC2

-

-

-0.06


(-0.21, 0.09)


Cannabis Use Disorder * PC3

-

-

-0.08


(-0.26, 0.11)


Cannabis Use Disorder * PC4

-

-

0.11


(-0.07, 0.28)


Cannabis Use Disorder * PC5

-

-

-0.03


(-0.19, 0.14)


Cannabis Use Disorder * PC6

-

-

0.19*


( 0.02, 0.37)


Cannabis Use Disorder * PC7

-

-

0.03


(-0.16, 0.21)


Cannabis Use Disorder * PC8

-

-

0.03


(-0.18, 0.23)


Cannabis Use Disorder * PC9

-

-

-0.06


(-0.27, 0.15)


Cannabis Use Disorder * PC10

-

-

0.05


(-0.14, 0.25)


Cannabis Use Disorder * Sex

-

-

0.06


(-0.31, 0.44)


Cannabis Use Disorder * Cohort

-

-

0.33


(-1.38, 2.04)


Cannabis Use Disorder * Age

-

-

0.00


(-0.84, 0.85)


Cannabis Use Disorder * Zygosity

-

-

0.12


(-0.20, 0.45)





B. Unusual Beliefs & Experiences


Predictors

Unusual Beliefs & Experiences

1

2

3


SCHZ-PGS

0.08**

0.07*

0.17


(0.03, 0.14)

(0.02, 0.13)

(-0.09, 0.43)


Cannabis Use Index

-

0.12***

0.10


(0.07, 0.18)

(-0.17, 0.36)


SCHZ-PGS * Cannabis Use Index

-

-

0.01


(-0.05, 0.07)


PC1

-0.02

-0.02

-0.01


(-0.08, 0.04)

(-0.08, 0.03)

(-0.08, 0.06)


PC2

0.02

0.02

0.02


(-0.04, 0.08)

(-0.04, 0.07)

(-0.04, 0.07)


PC3

0.06

0.06*

0.05


(-0.00, 0.11)

( 0.00, 0.12)

(-0.01, 0.11)


PC4

-0.03

-0.04

-0.06


(-0.09, 0.02)

(-0.10, 0.01)

(-0.12, 0.00)


PC5

0.03

0.03

0.02


(-0.02, 0.09)

(-0.03, 0.08)

(-0.05, 0.08)


PC6

-0.02

-0.02

0.00


(-0.08, 0.03)

(-0.07, 0.04)

(-0.05, 0.06)


PC7

-0.03

-0.03

-0.02


(-0.09, 0.02)

(-0.09, 0.02)

(-0.08, 0.04)


PC8

-0.04

-0.04

-0.04


(-0.10, 0.02)

(-0.09, 0.02)

(-0.10, 0.02)


PC9

0.01

0.01

-0.00


(-0.05, 0.06)

(-0.05, 0.06)

(-0.06, 0.06)


PC10

-0.01

-0.01

-0.01


(-0.07, 0.04)

(-0.07, 0.05)

(-0.07, 0.05)


Sex (ref: female)

0.31***

0.30***

0.28***


( 0.18, 0.44)

( 0.17, 0.43)

( 0.15, 0.42)


Cohort (ref: Cohort 2)

-0.04

-0.10

-0.08


(-0.63, 0.55)

(-0.68, 0.49)

(-0.67, 0.51)


Age

-0.14

-0.18

-0.17


(-0.44, 0.15)

(-0.47, 0.12)

(-0.46, 0.13)


Zygosity (ref: DZ)

-0.05

-0.04

-0.03


(-0.16, 0.07)

(-0.15, 0.08)

(-0.14, 0.09)


SCHZ-PGS * PC1

-

-

-0.02


(-0.08, 0.03)


SCHZ-PGS * PC2

-

-

-0.01


(-0.06, 0.05)


SCHZ-PGS * PC3

-

-

-0.01


(-0.07, 0.04)


SCHZ-PGS * PC4

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC5

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC6

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * PC7

-

-

-0.03


(-0.09, 0.02)


SCHZ-PGS * PC8

-

-

0.03


(-0.03, 0.10)


SCHZ-PGS * PC9

-

-

0.02


(-0.05, 0.09)


SCHZ-PGS * PC10

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * Sex

-

-

-0.05


(-0.18, 0.08)


SCHZ-PGS * Cohort

-

-

-0.15


(-0.75, 0.45)


SCHZ-PGS * Age

-

-

-0.02


(-0.32, 0.28)


SCHZ-PGS * Zygosity

-

-

0.05


(-0.06, 0.17)


Cannabis Use Index * PC1

-

-

0.09**


( 0.03, 0.14)


Cannabis Use Index * PC2

-

-

-0.04


(-0.09, 0.01)


Cannabis Use Index * PC3

-

-

-0.05


(-0.12, 0.01)


Cannabis Use Index * PC4

-

-

0.01


(-0.05, 0.07)


Cannabis Use Index * PC5

-

-

0.02


(-0.04, 0.08)


Cannabis Use Index * PC6

-

-

0.05


(-0.01, 0.10)


Cannabis Use Index * PC7

-

-

0.02


(-0.05, 0.09)


Cannabis Use Index * PC8

-

-

-0.07


(-0.14, 0.00)


Cannabis Use Index * PC9

-

-

-0.03


(-0.10, 0.05)


Cannabis Use Index * PC10

-

-

0.02


(-0.06, 0.10)


Cannabis Use Index * Sex

-

-

-0.06


(-0.19, 0.07)


Cannabis Use Index * Cohort

-

-

0.13


(-0.43, 0.69)


Cannabis Use Index * Age

-

-

0.06


(-0.22, 0.34)


Cannabis Use Index * Zygosity

-

-

0.05


(-0.06, 0.17)





Predictors

Unusual Beliefs & Experiences

1

2

3


SCHZ-PGS

0.08**

0.06*

0.15


(0.02, 0.14)

(0.01, 0.12)

(-0.12, 0.41)


Cannabis Use Disorder

-

0.26**

-0.23


(0.10, 0.41)

(-1.02, 0.57)


SCHZ-PGS * Cannabis Use Disorder

-

-

-0.04


(-0.20, 0.12)


PC1

-0.02

-0.03

-0.04


(-0.08, 0.04)

(-0.08, 0.03)

(-0.11, 0.03)


PC2

0.02

0.02

0.02


(-0.04, 0.08)

(-0.04, 0.07)

(-0.04, 0.08)


PC3

0.06

0.06*

0.07*


(-0.00, 0.11)

( 0.01, 0.12)

( 0.00, 0.13)


PC4

-0.03

-0.04

-0.06*


(-0.09, 0.02)

(-0.10, 0.01)

(-0.12, -0.00)


PC5

0.03

0.02

0.02


(-0.02, 0.09)

(-0.03, 0.08)

(-0.05, 0.09)


PC6

-0.02

-0.02

-0.02


(-0.08, 0.03)

(-0.07, 0.04)

(-0.08, 0.04)


PC7

-0.03

-0.03

-0.03


(-0.09, 0.02)

(-0.09, 0.02)

(-0.09, 0.03)


PC8

-0.04

-0.03

-0.03


(-0.10, 0.02)

(-0.09, 0.02)

(-0.09, 0.03)


PC9

0.01

0.01

0.01


(-0.05, 0.06)

(-0.05, 0.06)

(-0.05, 0.07)


PC10

-0.01

-0.01

-0.02


(-0.07, 0.04)

(-0.07, 0.04)

(-0.08, 0.04)


Sex (ref: female)

0.31***

0.30***

0.29***


( 0.18, 0.44)

( 0.17, 0.43)

( 0.15, 0.43)


Cohort (ref: Cohort 2)

-0.04

-0.03

-0.09


(-0.63, 0.55)

(-0.62, 0.57)

(-0.73, 0.55)


Age

-0.14

-0.15

-0.16


(-0.44, 0.15)

(-0.45, 0.15)

(-0.48, 0.16)


Zygosity (ref: DZ)

-0.05

-0.02

-0.04


(-0.16, 0.07)

(-0.13, 0.10)

(-0.16, 0.09)


SCHZ-PGS * PC1

-

-

-0.03


(-0.08, 0.03)


SCHZ-PGS * PC2

-

-

-0.02


(-0.08, 0.04)


SCHZ-PGS * PC3

-

-

-0.01


(-0.06, 0.05)


SCHZ-PGS * PC4

-

-

0.01


(-0.05, 0.07)


SCHZ-PGS * PC5

-

-

0.00


(-0.06, 0.06)


SCHZ-PGS * PC6

-

-

0.02


(-0.04, 0.07)


SCHZ-PGS * PC7

-

-

-0.03


(-0.09, 0.03)


SCHZ-PGS * PC8

-

-

0.02


(-0.04, 0.09)


SCHZ-PGS * PC9

-

-

0.01


(-0.06, 0.08)


SCHZ-PGS * PC10

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * Sex

-

-

-0.03


(-0.17, 0.10)


SCHZ-PGS * Cohort

-

-

-0.21


(-0.82, 0.39)


SCHZ-PGS * Age

-

-

-0.06


(-0.36, 0.25)


SCHZ-PGS * Zygosity

-

-

0.07


(-0.05, 0.19)


Cannabis Use Disorder * PC1

-

-

0.17*


( 0.01, 0.33)


Cannabis Use Disorder * PC2

-

-

0.04


(-0.11, 0.19)


Cannabis Use Disorder * PC3

-

-

-0.04


(-0.23, 0.15)


Cannabis Use Disorder * PC4

-

-

0.07


(-0.11, 0.25)


Cannabis Use Disorder * PC5

-

-

-0.01


(-0.17, 0.16)


Cannabis Use Disorder * PC6

-

-

0.13


(-0.05, 0.30)


Cannabis Use Disorder * PC7

-

-

0.03


(-0.16, 0.23)


Cannabis Use Disorder * PC8

-

-

0.03


(-0.18, 0.23)


Cannabis Use Disorder * PC9

-

-

-0.00


(-0.21, 0.21)


Cannabis Use Disorder * PC10

-

-

0.06


(-0.14, 0.25)


Cannabis Use Disorder * Sex

-

-

0.06


(-0.31, 0.44)


Cannabis Use Disorder * Cohort

-

-

0.79


(-0.94, 2.52)


Cannabis Use Disorder * Age

-

-

0.24


(-0.61, 1.09)


Cannabis Use Disorder * Zygosity

-

-

0.15


(-0.18, 0.48)





C. Eccentricity


Predictors

Eccentricity

1

2

3


SCHZ-PGS

0.06*

0.06

0.10


(0.01, 0.12)

(0.00, 0.11)

(-0.17, 0.37)


Cannabis Use Index

-

0.09***

0.13


(0.04, 0.14)

(-0.14, 0.39)


SCHZ-PGS * Cannabis Use Index

-

-

0.04


(-0.02, 0.10)


PC1

0.00

0.00

0.04


(-0.06, 0.06)

(-0.06, 0.06)

(-0.04, 0.11)


PC2

-0.01

-0.01

-0.01


(-0.06, 0.05)

(-0.07, 0.05)

(-0.07, 0.05)


PC3

0.01

0.02

-0.00


(-0.05, 0.07)

(-0.04, 0.08)

(-0.07, 0.06)


PC4

-0.04

-0.04

-0.06


(-0.09, 0.02)

(-0.10, 0.02)

(-0.12, 0.00)


PC5

0.05

0.04

0.05


(-0.01, 0.10)

(-0.02, 0.10)

(-0.01, 0.12)


PC6

-0.02

-0.01

0.00


(-0.08, 0.04)

(-0.07, 0.04)

(-0.06, 0.06)


PC7

-0.04

-0.04

-0.03


(-0.10, 0.02)

(-0.10, 0.02)

(-0.09, 0.03)


PC8

-0.02

-0.02

-0.02


(-0.08, 0.04)

(-0.08, 0.04)

(-0.08, 0.05)


PC9

0.02

0.02

-0.00


(-0.04, 0.07)

(-0.04, 0.08)

(-0.06, 0.06)


PC10

-0.01

-0.01

-0.02


(-0.07, 0.05)

(-0.07, 0.05)

(-0.08, 0.05)


Sex (ref: female)

0.39***

0.37***

0.35***


( 0.25, 0.52)

( 0.24, 0.51)

( 0.21, 0.48)


Cohort (ref: Cohort 2)

-0.28

-0.33

-0.27


(-0.90, 0.33)

(-0.94, 0.28)

(-0.88, 0.34)


Age

-0.35*

-0.38*

-0.35*


(-0.66, -0.05)

(-0.68, -0.07)

(-0.65, -0.04)


Zygosity (ref: DZ)

-0.06

-0.05

-0.04


(-0.18, 0.06)

(-0.17, 0.07)

(-0.16, 0.08)


SCHZ-PGS * PC1

-

-

-0.06*


(-0.11, -0.01)


SCHZ-PGS * PC2

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * PC3

-

-

-0.03


(-0.09, 0.03)


SCHZ-PGS * PC4

-

-

0.01


(-0.06, 0.07)


SCHZ-PGS * PC5

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC6

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * PC7

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC8

-

-

0.04


(-0.02, 0.10)


SCHZ-PGS * PC9

-

-

0.04


(-0.03, 0.11)


SCHZ-PGS * PC10

-

-

0.05


(-0.02, 0.11)


SCHZ-PGS * Sex

-

-

0.02


(-0.11, 0.15)


SCHZ-PGS * Cohort

-

-

-0.13


(-0.74, 0.49)


SCHZ-PGS * Age

-

-

-0.01


(-0.32, 0.30)


SCHZ-PGS * Zygosity

-

-

0.01


(-0.11, 0.13)


Cannabis Use Index * PC1

-

-

0.08**


( 0.03, 0.14)


Cannabis Use Index * PC2

-

-

-0.07*


(-0.12, -0.01)


Cannabis Use Index * PC3

-

-

-0.03


(-0.09, 0.04)


Cannabis Use Index * PC4

-

-

0.01


(-0.05, 0.07)


Cannabis Use Index * PC5

-

-

-0.00


(-0.06, 0.06)


Cannabis Use Index * PC6

-

-

0.09**


( 0.03, 0.15)


Cannabis Use Index * PC7

-

-

0.02


(-0.04, 0.09)


Cannabis Use Index * PC8

-

-

-0.05


(-0.12, 0.03)


Cannabis Use Index * PC9

-

-

-0.06


(-0.14, 0.01)


Cannabis Use Index * PC10

-

-

-0.00


(-0.08, 0.08)


Cannabis Use Index * Sex

-

-

-0.02


(-0.15, 0.11)


Cannabis Use Index * Cohort

-

-

-0.12


(-0.68, 0.44)


Cannabis Use Index * Age

-

-

-0.06


(-0.34, 0.21)


Cannabis Use Index * Zygosity

-

-

0.03


(-0.08, 0.14)





Predictors

Eccentricity

1

2

3


SCHZ-PGS

0.06*

0.06*

0.07


(0.01, 0.12)

(0.00, 0.12)

(-0.20, 0.35)


Cannabis Use Disorder

-

0.23**

0.39


(0.08, 0.39)

(-0.41, 1.18)


SCHZ-PGS * Cannabis Use Disorder

-

-

0.12


(-0.04, 0.28)


PC1

0.00

-0.01

0.00


(-0.06, 0.06)

(-0.06, 0.05)

(-0.07, 0.08)


PC2

-0.01

-0.01

0.01


(-0.06, 0.05)

(-0.07, 0.05)

(-0.06, 0.07)


PC3

0.01

0.02

0.02


(-0.05, 0.07)

(-0.04, 0.08)

(-0.05, 0.08)


PC4

-0.04

-0.05

-0.08*


(-0.09, 0.02)

(-0.10, 0.01)

(-0.14, -0.01)


PC5

0.05

0.04

0.05


(-0.01, 0.10)

(-0.02, 0.10)

(-0.02, 0.12)


PC6

-0.02

-0.01

-0.03


(-0.08, 0.04)

(-0.07, 0.05)

(-0.09, 0.03)


PC7

-0.04

-0.04

-0.04


(-0.10, 0.02)

(-0.10, 0.02)

(-0.10, 0.02)


PC8

-0.02

-0.02

-0.00


(-0.08, 0.04)

(-0.08, 0.04)

(-0.06, 0.06)


PC9

0.02

0.02

0.02


(-0.04, 0.07)

(-0.04, 0.08)

(-0.04, 0.09)


PC10

-0.01

-0.01

-0.02


(-0.07, 0.05)

(-0.07, 0.05)

(-0.08, 0.05)


Sex (ref: female)

0.39***

0.37***

0.34***


( 0.25, 0.52)

( 0.23, 0.50)

( 0.19, 0.48)


Cohort (ref: Cohort 2)

-0.28

-0.23

-0.10


(-0.90, 0.33)

(-0.85, 0.39)

(-0.76, 0.56)


Age

-0.35*

-0.33*

-0.25


(-0.66, -0.05)

(-0.65, -0.02)

(-0.58, 0.09)


Zygosity (ref: DZ)

-0.06

-0.04

-0.05


(-0.18, 0.06)

(-0.16, 0.08)

(-0.18, 0.08)


SCHZ-PGS * PC1

-

-

-0.06*


(-0.11, -0.00)


SCHZ-PGS * PC2

-

-

0.01


(-0.05, 0.07)


SCHZ-PGS * PC3

-

-

-0.03


(-0.08, 0.03)


SCHZ-PGS * PC4

-

-

0.01


(-0.06, 0.07)


SCHZ-PGS * PC5

-

-

-0.00


(-0.06, 0.06)


SCHZ-PGS * PC6

-

-

0.03


(-0.02, 0.09)


SCHZ-PGS * PC7

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC8

-

-

0.04


(-0.02, 0.11)


SCHZ-PGS * PC9

-

-

0.05


(-0.02, 0.12)


SCHZ-PGS * PC10

-

-

0.05


(-0.01, 0.11)


SCHZ-PGS * Sex

-

-

0.03


(-0.11, 0.16)


SCHZ-PGS * Cohort

-

-

-0.10


(-0.72, 0.52)


SCHZ-PGS * Age

-

-

0.01


(-0.30, 0.32)


SCHZ-PGS * Zygosity

-

-

0.01


(-0.11, 0.13)


Cannabis Use Disorder * PC1

-

-

0.15


(-0.01, 0.31)


Cannabis Use Disorder * PC2

-

-

-0.13


(-0.28, 0.02)


Cannabis Use Disorder * PC3

-

-

-0.06


(-0.25, 0.13)


Cannabis Use Disorder * PC4

-

-

0.08


(-0.10, 0.26)


Cannabis Use Disorder * PC5

-

-

-0.01


(-0.17, 0.16)


Cannabis Use Disorder * PC6

-

-

0.22*


( 0.04, 0.40)


Cannabis Use Disorder * PC7

-

-

0.03


(-0.16, 0.22)


Cannabis Use Disorder * PC8

-

-

-0.04


(-0.25, 0.16)


Cannabis Use Disorder * PC9

-

-

-0.14


(-0.35, 0.07)


Cannabis Use Disorder * PC10

-

-

0.03


(-0.17, 0.22)


Cannabis Use Disorder * Sex

-

-

0.05


(-0.33, 0.43)


Cannabis Use Disorder * Cohort

-

-

-0.57


(-2.30, 1.16)


Cannabis Use Disorder * Age

-

-

-0.39


(-1.25, 0.46)


Cannabis Use Disorder * Zygosity

-

-

0.14


(-0.19, 0.47)





D. Perceptual Dysregulation


Predictors

Eccentricity

1

2

3


SCHZ-PGS

0.09**

0.08**

0.27


(0.03, 0.15)

(0.02, 0.14)

(0.00, 0.54)


Cannabis Use Index

-

0.14***

0.08


(0.09, 0.20)

(-0.18, 0.35)


SCHZ-PGS * Cannabis Use Index

-

-

0.02


(-0.04, 0.08)


PC1

0.01

0.00

0.02


(-0.05, 0.07)

(-0.05, 0.06)

(-0.06, 0.09)


PC2

0.03

0.03

0.03


(-0.03, 0.09)

(-0.03, 0.08)

(-0.03, 0.09)


PC3

0.03

0.03

0.01


(-0.03, 0.09)

(-0.02, 0.09)

(-0.05, 0.08)


PC4

-0.02

-0.03

-0.05


(-0.07, 0.04)

(-0.08, 0.03)

(-0.11, 0.01)


PC5

0.04

0.03

0.03


(-0.02, 0.10)

(-0.02, 0.09)

(-0.04, 0.10)


PC6

-0.01

-0.01

0.00


(-0.07, 0.04)

(-0.07, 0.05)

(-0.06, 0.06)


PC7

-0.04

-0.04

-0.03


(-0.10, 0.02)

(-0.10, 0.02)

(-0.09, 0.03)


PC8

-0.02

-0.01

-0.01


(-0.08, 0.04)

(-0.07, 0.04)

(-0.07, 0.05)


PC9

0.03

0.03

0.03


(-0.03, 0.09)

(-0.03, 0.09)

(-0.03, 0.09)


PC10

-0.04

-0.03

-0.04


(-0.10, 0.02)

(-0.09, 0.02)

(-0.10, 0.02)


Sex (ref: female)

0.26***

0.24***

0.21**


( 0.12, 0.39)

( 0.11, 0.37)

( 0.08, 0.35)


Cohort (ref: Cohort 2)

-0.41

-0.49

-0.40


(-1.03, 0.20)

(-1.09, 0.12)

(-1.01, 0.20)


Age

-0.41**

-0.45**

-0.41**


(-0.72, -0.10)

(-0.76, -0.15)

(-0.72, -0.10)


Zygosity (ref: DZ)

-0.06

-0.05

-0.03


(-0.18, 0.06)

(-0.17, 0.07)

(-0.15, 0.09)


SCHZ-PGS * PC1

-

-

-0.03


(-0.09, 0.02)


SCHZ-PGS * PC2

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * PC3

-

-

-0.04


(-0.10, 0.01)


SCHZ-PGS * PC4

-

-

0.03


(-0.03, 0.09)


SCHZ-PGS * PC5

-

-

-0.03


(-0.09, 0.03)


SCHZ-PGS * PC6

-

-

0.02


(-0.03, 0.08)


SCHZ-PGS * PC7

-

-

0.00


(-0.06, 0.06)


SCHZ-PGS * PC8

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * PC9

-

-

0.00


(-0.07, 0.07)


SCHZ-PGS * PC10

-

-

-0.01


(-0.08, 0.05)


SCHZ-PGS * Sex

-

-

0.06


(-0.07, 0.20)


SCHZ-PGS * Cohort

-

-

-0.54


(-1.16, 0.07)


SCHZ-PGS * Age

-

-

-0.23


(-0.54, 0.08)


SCHZ-PGS * Zygosity

-

-

0.06


(-0.06, 0.18)


Cannabis Use Index * PC1

-

-

0.08**


( 0.03, 0.13)


Cannabis Use Index * PC2

-

-

-0.06*


(-0.11, -0.01)


Cannabis Use Index * PC3

-

-

-0.03


(-0.09, 0.04)


Cannabis Use Index * PC4

-

-

-0.01


(-0.08, 0.05)


Cannabis Use Index * PC5

-

-

0.03


(-0.03, 0.09)


Cannabis Use Index * PC6

-

-

0.06*


( 0.01, 0.12)


Cannabis Use Index * PC7

-

-

0.02


(-0.05, 0.09)


Cannabis Use Index * PC8

-

-

0.02


(-0.06, 0.09)


Cannabis Use Index * PC9

-

-

-0.02


(-0.10, 0.05)


Cannabis Use Index * PC10

-

-

0.00


(-0.07, 0.08)


Cannabis Use Index * Sex

-

-

-0.09


(-0.22, 0.04)


Cannabis Use Index * Cohort

-

-

0.18


(-0.39, 0.75)


Cannabis Use Index * Age

-

-

0.06


(-0.22, 0.34)


Cannabis Use Index * Zygosity

-

-

0.03


(-0.08, 0.14)





Predictors

Perceptual Dysregulation

1

2

3


SCHZ-PGS

0.09**

0.08**

0.28*


(0.03, 0.15)

(0.02, 0.14)

(0.00, 0.55)


Cannabis Use Disorder

-

0.29***

-0.30


(0.13, 0.45)

(-1.11, 0.51)


SCHZ-PGS * Cannabis Use Disorder

-

-

0.17*


(0.01, 0.34)


PC1

0.01

-0.00

-0.02


(-0.05, 0.07)

(-0.06, 0.05)

(-0.09, 0.06)


PC2

0.03

0.03

0.04


(-0.03, 0.09)

(-0.03, 0.09)

(-0.02, 0.10)


PC3

0.03

0.03

0.03


(-0.03, 0.09)

(-0.03, 0.09)

(-0.03, 0.10)


PC4

-0.02

-0.03

-0.07*


(-0.07, 0.04)

(-0.09, 0.03)

(-0.13, -0.00)


PC5

0.04

0.04

0.03


(-0.02, 0.10)

(-0.02, 0.10)

(-0.04, 0.10)


PC6

-0.01

-0.01

-0.03


(-0.07, 0.04)

(-0.07, 0.05)

(-0.09, 0.04)


PC7

-0.04

-0.04

-0.03


(-0.10, 0.02)

(-0.09, 0.02)

(-0.10, 0.03)


PC8

-0.02

-0.02

-0.02


(-0.08, 0.04)

(-0.08, 0.04)

(-0.09, 0.04)


PC9

0.03

0.03

0.04


(-0.03, 0.09)

(-0.03, 0.09)

(-0.03, 0.10)


PC10

-0.04

-0.04

-0.05


(-0.10, 0.02)

(-0.10, 0.02)

(-0.12, 0.01)


Sex (ref: female)

0.26***

0.24***

0.22**


( 0.12, 0.39)

( 0.10, 0.38)

( 0.07, 0.37)


Cohort (ref: Cohort 2)

-0.41

-0.35

-0.38


(-1.03, 0.20)

(-0.97, 0.27)

(-1.04, 0.29)


Age

-0.41**

-0.39*

-0.38*


(-0.72, -0.10)

(-0.70, -0.08)

(-0.71, -0.04)


Zygosity (ref: DZ)

-0.06

-0.04

-0.04


(-0.18, 0.06)

(-0.17, 0.08)

(-0.17, 0.09)


SCHZ-PGS * PC1

-

-

-0.03


(-0.09, 0.02)


SCHZ-PGS * PC2

-

-

0.01


(-0.05, 0.07)


SCHZ-PGS * PC3

-

-

-0.03


(-0.09, 0.02)


SCHZ-PGS * PC4

-

-

0.03


(-0.04, 0.09)


SCHZ-PGS * PC5

-

-

-0.01


(-0.07, 0.05)


SCHZ-PGS * PC6

-

-

0.02


(-0.03, 0.08)


SCHZ-PGS * PC7

-

-

0.01


(-0.05, 0.06)


SCHZ-PGS * PC8

-

-

0.02


(-0.04, 0.08)


SCHZ-PGS * PC9

-

-

0.01


(-0.06, 0.08)


SCHZ-PGS * PC10

-

-

-0.01


(-0.08, 0.05)


SCHZ-PGS * Sex

-

-

0.07


(-0.06, 0.21)


SCHZ-PGS * Cohort

-

-

-0.61


(-1.24, 0.01)


SCHZ-PGS * Age

-

-

-0.26


(-0.58, 0.05)


SCHZ-PGS * Zygosity

-

-

0.07


(-0.05, 0.19)


Cannabis Use Disorder * PC1

-

-

0.19*


( 0.03, 0.35)


Cannabis Use Disorder * PC2

-

-

-0.04


(-0.19, 0.11)


Cannabis Use Disorder * PC3

-

-

-0.11


(-0.30, 0.08)


Cannabis Use Disorder * PC4

-

-

0.15


(-0.03, 0.33)


Cannabis Use Disorder * PC5

-

-

-0.06


(-0.23, 0.11)


Cannabis Use Disorder * PC6

-

-

0.14


(-0.04, 0.32)


Cannabis Use Disorder * PC7

-

-

-0.00


(-0.20, 0.19)


Cannabis Use Disorder * PC8

-

-

0.15


(-0.06, 0.36)


Cannabis Use Disorder * PC9

-

-

0.02


(-0.20, 0.23)


Cannabis Use Disorder * PC10

-

-

0.08


(-0.12, 0.28)


Cannabis Use Disorder * Sex

-

-

0.03


(-0.36, 0.41)


Cannabis Use Disorder * Cohort

-

-

1.09


(-0.67, 2.85)


Cannabis Use Disorder * Age

-

-

0.36


(-0.51, 1.23)


Cannabis Use Disorder * Zygosity

-

-

0.04


(-0.29, 0.38)



Notes. Tables show results from individual-level models testing for (1) associations between polygenic risk of schizophrenia (SCHZ-PGS) and adult Psychoticism, (2) incremental contributions to Psychoticism from adolescent cannabis exposure and polygenic risk of schizophrenia, and (3) interactions between adolescent cannabis exposure and polygenic risk of schizophrenia. Estimates for continuous predictors are reported as standardized betas with 95% confidence intervals, reflecting the standard deviation increase in each outcome associated with a standard deviation increase in each predictor. Estimates for binary predictors are standardized betas with 95% confidence intervals reflecting the difference in each outcome associated with scoring a “1” on this variable (vs. “0” for the reference category). All models included participant age, sex, zygosity, cohort, and the first 10 genetic principal components (PCs) as covariates. Models testing for interaction between polygenic risk of schizophrenia and cannabis exposure additionally included terms adjusting for possible interactions between the schizophrenia PGS or cannabis exposure measures with covariates. *p<0.05, **p<0.01, ***p<0.001


Supplemental Figure 1. Kernel density plot showing the distribution of schizophrenia polygenic risk scores for twin participants both with and without adolescent cannabis use disorder diagnoses.



Notes. Solid red line depicts density plot of schizophrenia polygenic risk scores for twins who met criteria for an adolescent cannabis use disorder diagnosis (n = 169). Dotted green line depicts the corresponding density plot for twins who did not meet criteria (n = 1122). The shape and extent of overlap of the two distributions suggests similar levels of polygenic risk in both groups.