Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence

Marieke Hiemstra; Stefanie A. Nelemans; Susan Branje; Kristel R. van Eijk; Jouke Jan Hottenga; Christiaan H. Vinkers; Pol van Lier; Wim Meeus; Marco P. Boks

doi:10.1016/j.drugalcdep.2018.05.024

Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence

Marieke Hiemstra^*
, Stefanie A. Nelemans
, Susan Branje
, Kristel R. van Eijk
, Jouke Jan Hottenga
, Christiaan H. Vinkers
, Pol van Lier
, Wim Meeus
, Marco P. Boks

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

Background: Previously reported comorbidity between schizophrenia and substance use may be explained by shared underlying risk factors, such as genetic background. The aim of the present longitudinal study was to investigate how a genetic predisposition to schizophrenia was associated with patterns of substance use (cannabis use, smoking, alcohol use) during adolescence (comparing ages 13–16 with 16–20 years). Method: Using piecewise latent growth curve modelling in a longitudinal adolescent cohort (RADAR-Y study, N = 372), we analyzed the association of polygenic risk scores for schizophrenia (PRS; p-value thresholds (p_t) < 5e-8 to p_t < 0.5) with increase in substance use over the years, including stratified analyses for gender. Significance thresholds were set to adjust for multiple testing using Bonferroni at p ≤ 0.001. Results: High schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16–20 (PRS thresholds p_t < 5e-5 and p_t < 5e-4; p_t < 5e-6 was marginally significant), whereas more lenient PRS thresholds (PRS thresholds p_t < 5e-3 to p_t < 0.5) showed the reverse association. For smoking and alcohol, no clear relations were found. Conclusions: In conclusion, our findings support a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.

Original language	English
Pages (from-to)	143-150
Number of pages	8
Journal	Drug and Alcohol Dependence
Volume	190
Early online date	30 Jun 2018
DOIs	https://doi.org/10.1016/j.drugalcdep.2018.05.024
Publication status	Published - 1 Sept 2018

Funding

This work was supported by a Dynamics of Youth grant from the University Utrecht, the Netherlands. Data from the Research on Adolescent Development and Relationships (RADAR) study were used. RADAR has been financially supported by main grants from the Netherlands Organisation for Scientific Research (GB-MAGW 480-03-005, GB-MAGW 480-08-006), the Stichting Achmea Slachtoffer en Samenleving (SASS), a grant from the Netherlands Organisation for Scientific Research to the Consortium Individual Development (CID; 024.001.003), and various other grants from the Netherlands Organisation for Scientific Research, the VU University Amsterdam, and Utrecht University. The funding sources had no further role in study design, the collection, analysis, and interpretation of data, the writing of the report, or in the decision to submit the paper for publication.

Funders	Funder number
Stichting Achmea Slachtoffer en Samenleving	024.001.003
University Utrecht
Universiteit Utrecht
Vrije Universiteit Amsterdam
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	GB-MAGW 480-03-005, GB-MAGW 480-08-006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adolescence
Alcohol use
Cannabis use
Genetic
Polygenic risk score
Schizophrenia
Smoking
Substance use

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Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescenceFinal published version, 351 KBLicence: Article 25fa Dutch Copyright Act

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title = "Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence",

abstract = "Background: Previously reported comorbidity between schizophrenia and substance use may be explained by shared underlying risk factors, such as genetic background. The aim of the present longitudinal study was to investigate how a genetic predisposition to schizophrenia was associated with patterns of substance use (cannabis use, smoking, alcohol use) during adolescence (comparing ages 13–16 with 16–20 years). Method: Using piecewise latent growth curve modelling in a longitudinal adolescent cohort (RADAR-Y study, N = 372), we analyzed the association of polygenic risk scores for schizophrenia (PRS; p-value thresholds (pt) < 5e-8 to pt < 0.5) with increase in substance use over the years, including stratified analyses for gender. Significance thresholds were set to adjust for multiple testing using Bonferroni at p ≤ 0.001. Results: High schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16–20 (PRS thresholds pt < 5e-5 and pt < 5e-4; pt < 5e-6 was marginally significant), whereas more lenient PRS thresholds (PRS thresholds pt < 5e-3 to pt < 0.5) showed the reverse association. For smoking and alcohol, no clear relations were found. Conclusions: In conclusion, our findings support a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.",

keywords = "Adolescence, Alcohol use, Cannabis use, Genetic, Polygenic risk score, Schizophrenia, Smoking, Substance use",

author = "Marieke Hiemstra and Nelemans, \{Stefanie A.\} and Susan Branje and \{van Eijk\}, \{Kristel R.\} and Hottenga, \{Jouke Jan\} and Vinkers, \{Christiaan H.\} and \{van Lier\}, Pol and Wim Meeus and Boks, \{Marco P.\}",

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doi = "10.1016/j.drugalcdep.2018.05.024",

language = "English",

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journal = "Drug and Alcohol Dependence",

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publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence

AU - Hiemstra, Marieke

AU - Nelemans, Stefanie A.

AU - Branje, Susan

AU - van Eijk, Kristel R.

AU - Hottenga, Jouke Jan

AU - Vinkers, Christiaan H.

AU - van Lier, Pol

AU - Meeus, Wim

AU - Boks, Marco P.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Previously reported comorbidity between schizophrenia and substance use may be explained by shared underlying risk factors, such as genetic background. The aim of the present longitudinal study was to investigate how a genetic predisposition to schizophrenia was associated with patterns of substance use (cannabis use, smoking, alcohol use) during adolescence (comparing ages 13–16 with 16–20 years). Method: Using piecewise latent growth curve modelling in a longitudinal adolescent cohort (RADAR-Y study, N = 372), we analyzed the association of polygenic risk scores for schizophrenia (PRS; p-value thresholds (pt) < 5e-8 to pt < 0.5) with increase in substance use over the years, including stratified analyses for gender. Significance thresholds were set to adjust for multiple testing using Bonferroni at p ≤ 0.001. Results: High schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16–20 (PRS thresholds pt < 5e-5 and pt < 5e-4; pt < 5e-6 was marginally significant), whereas more lenient PRS thresholds (PRS thresholds pt < 5e-3 to pt < 0.5) showed the reverse association. For smoking and alcohol, no clear relations were found. Conclusions: In conclusion, our findings support a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.

AB - Background: Previously reported comorbidity between schizophrenia and substance use may be explained by shared underlying risk factors, such as genetic background. The aim of the present longitudinal study was to investigate how a genetic predisposition to schizophrenia was associated with patterns of substance use (cannabis use, smoking, alcohol use) during adolescence (comparing ages 13–16 with 16–20 years). Method: Using piecewise latent growth curve modelling in a longitudinal adolescent cohort (RADAR-Y study, N = 372), we analyzed the association of polygenic risk scores for schizophrenia (PRS; p-value thresholds (pt) < 5e-8 to pt < 0.5) with increase in substance use over the years, including stratified analyses for gender. Significance thresholds were set to adjust for multiple testing using Bonferroni at p ≤ 0.001. Results: High schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16–20 (PRS thresholds pt < 5e-5 and pt < 5e-4; pt < 5e-6 was marginally significant), whereas more lenient PRS thresholds (PRS thresholds pt < 5e-3 to pt < 0.5) showed the reverse association. For smoking and alcohol, no clear relations were found. Conclusions: In conclusion, our findings support a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.

KW - Adolescence

KW - Alcohol use

KW - Cannabis use

KW - Genetic

KW - Polygenic risk score

KW - Schizophrenia

KW - Smoking

KW - Substance use

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SP - 143

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JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

ER -

Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence

Abstract

Funding

UN SDGs

Keywords

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