DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Cannabis use. The EFO term Cannabis use was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: Cannabis use

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

S Stringer, CC Minică, KJ Verweij, H Mbarek, M Bernard, J Derringer, KR van Eijk, JD Isen, A Loukola, DF Maciejewski, E Mihailov, PJ van der Most, C Sánchez-Mora, L Roos, R Sherva, R Walters, JJ Ware, A Abdellaoui, TB Bigdeli, SJ Branje, SA Brown, M Bruinenberg, M Casas, T Esko, I Garcia-Martinez, SD Gordon, JM Harris, CA Hartman, AK Henders, AC Heath, IB Hickie, M Hickman, CJ Hopfer, JJ Hottenga, AC Huizink, DE Irons, RS Kahn, T Korhonen, HR Kranzler, K Krauter, PA van Lier, GH Lubke, PA Madden, R Mägi, MK McGue, SE Medland, WH Meeus, MB Miller, GW Montgomery, MG Nivard, IM Nolte, AJ Oldehinkel, Z Pausova, B Qaiser, L Quaye, JA Ramos-Quiroga, V Richarte, RJ Rose, J Shin, MC Stallings, AI Stiby, TL Wall, MJ Wright, HM Koot, T Paus, JK Hewitt, M Ribasés, J Kaprio, MP Boks, H Snieder, T Spector, MR Munafò, A Metspalu, J Gelernter, DI Boomsma, WG Iacono, NG Martin, NA Gillespie, EM Derks, JM Vink

TITLE:

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

JOURNAL:

Translational psychiatry Mar 2016, Vol 6, pp. e769

ABSTRACT:

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use. PUBMED: 27023175
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