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dc.contributor.authorMinica, CC
dc.contributor.authorVerweij, KJH
dc.contributor.authorvan der, Most PJ
dc.contributor.authorMbarek, H
dc.contributor.authorBernard, M
dc.contributor.authorvan Eijk, KR
dc.contributor.authorLind, PA
dc.contributor.authorLiu, MZ
dc.contributor.authorMaciejewski, DF
dc.contributor.authorPalviainen, T
dc.contributor.authorSánchez-Mora, C
dc.contributor.authorSherva, R
dc.contributor.authorTaylor, M
dc.contributor.authorWalters, RK
dc.contributor.authorAbdellaoui, A
dc.contributor.authorBigdeli, TB
dc.contributor.authorBranje, SJT
dc.contributor.authorBrown, SA
dc.contributor.authorCasas, M
dc.contributor.authorCorley, RP
dc.contributor.authoret al. [Incl Korhonen, Tellervo]
dc.date.accessioned2018-09-21T11:03:18Z
dc.date.available2018-09-21T11:03:18Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6936
dc.description.abstractBackground 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.
dc.publisherWiley
dc.relation.ispartofseriesADDICTION
dc.relation.urihttp://dx.doi.org/10.1111/add.14368
dc.rightsAll rights reserved
dc.subjectage at first use
dc.subjectATP2C2
dc.subjectcannabis initiation
dc.subjectgenome-wide association
dc.subjectheritability
dc.subjectsubstance use
dc.titleGenome-Wide Association Meta-Analysis of Age at First Cannabis Use
dc.description.versionfinal draft
dc.contributor.departmentSchool of Medicine / Public Health
uef.solecris.id55902553en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Society for the Study of Addiction
dc.relation.doi10.1111/add.14368
dc.description.reviewstatuspeerReviewed
dc.format.pagerange1-14
dc.relation.issn0965-2140
dc.relation.volume[Epub ahead of print 19 Aug 2018]
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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