Genome‐wide association meta‐analysis of age at first cannabis use.
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 id...
| Publicado en: | Addiction Vol. 113; no. 11; pp. 2073 - 2087 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Nov2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=132211589&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 132211589 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09652140 AIO jtl: Addiction issn: 09652140 maglogo: Y pubinfo: dt: Nov2018 vid: 113 iid: 11 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 132211589 132211589 132211589 10.1111/add.14368 132211589 ppf: 2073 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Genome‐wide association meta‐analysis of age at first cannabis use. aug: au: Minică, Camelia C. Verweij, Karin J. H. Most, Peter J. Mbarek, Hamdi Bernard, Manon Eijk, Kristel R. Lind, Penelope A. Liu, Meng Zhen Maciejewski, Dominique F. Palviainen, Teemu Sánchez‐Mora, Cristina Sherva, Richard Taylor, Michelle Walters, Raymond K. Abdellaoui, Abdel Bigdeli, Timothy B. Branje, Susan J. T. Brown, Sandra A. Casas, Miguel Corley, Robin P. affil: Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam the Netherlands sug: subj: Cannabis Polymorphism, Genetic Twins Age Factors Substance Use Disorders Familial and Genetic Substance Use Disorders Diagnosis Human Meta Analysis Prospective Studies Confidence Intervals Models, Statistical Europe North America Australia Chromosomes Carrier Proteins Analysis Cocaine Substance Dependence Calcium Signal Transduction Narcotics ab: 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. pubtype: Academic Journal doctype: meta analysis research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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