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Genome-Wide Association Meta-Analysis of Age at First Cannabis Use

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Rinnakkaistallenteen versio
final draft
Päivämäärä
2018
Tekijä
Minica, CC
Verweij, KJH
van der, Most PJ
Mbarek, H
Bernard, M
van Eijk, KR
Lind, PA
Liu, MZ
Maciejewski, DF
Palviainen, T
Sánchez-Mora, C
Sherva, R
Taylor, M
Walters, RK
Abdellaoui, A
Bigdeli, TB
Branje, SJT
Brown, SA
Casas, M
Corley, RP
et al. [Incl Korhonen, Tellervo]
Yksilöllinen tunniste
10.1111/add.14368
Metadata
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Rinnakkaistallennettu artikkeli

Viittaus
Minica, CC. Verweij, KJH. van der, Most PJ. Mbarek, H. Bernard, M. van Eijk, KR. Lind, PA. Liu, MZ. Maciejewski, DF. Palviainen, T. Sánchez-Mora, C. Sherva, R. Taylor, M. Walters, RK. Abdellaoui, A. Bigdeli, TB. Branje, SJT. Brown, SA. Casas, M. Corley, RP. et al. [Incl Korhonen, Tellervo]. (2018). Genome-Wide Association Meta-Analysis of Age at First Cannabis Use.  ADDICTION, [Epub ahead of print 19 Aug 2018], 1-14. 10.1111/add.14368.
Oikeudet
© Society for the Study of Addiction
Lisensointimalli
All rights reserved
Tiivistelmä

Background and aims
Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi‐substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.

Methods
A twin‐based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome‐wide association meta‐analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.

Results
The twin‐based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19–60%]. Shared and unique environmental factors explained 39% (95% CI = 20–56%) and 22% (95% CI = 16–29%). The genome‐wide association meta‐analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium‐transporting ATPase gene (ATP2C2) at P < 5E‐08. All five SNPs are in high linkage disequilibrium (LD) (r2 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E‐09). Gene‐based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e‐06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP‐based heritability for age at first cannabis use was non‐significant.

Conclusion
Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Avainsanat
age at first use   ATP2C2   cannabis initiation   genome-wide association   heritability   substance use   
URI
https://erepo.uef.fi/handle/123456789/6936
Linkki alkuperäiseen julkaisuun
http://dx.doi.org/10.1111/add.14368
Julkaisija
Wiley
Kokoelmat
  • Terveystieteiden tiedekunta
University of Eastern Finland
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erepo@uef.fi
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University of Eastern Finland
OpenAccess
eRepo
erepo@uef.fi
Lähetä palautetta
OpenUEF
Palvelun tarjoaa
Itä-Suomen yliopiston kirjasto
Library web pages
Twitter
Facebook
Youtube
Library blog