Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2016 Mar 29;6(3):e769.
doi: 10.1038/tp.2016.36.

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

S Stringer  1   2 , C C Minică  3 , K J H Verweij  3   4   5 , H Mbarek  3 , M Bernard  6 , J Derringer  7 , K R van Eijk  8 , J D Isen  9 , A Loukola  10 , D F Maciejewski  5 , E Mihailov  11 , P J van der Most  12 , C Sánchez-Mora  13   14   15 , L Roos  16 , R Sherva  17 , R Walters  18   19   20 , J J Ware  21   22 , A Abdellaoui  3 , T B Bigdeli  23 , S J T Branje  24 , S A Brown  25 , M Bruinenberg  26 , M Casas  14   15   27 , T Esko  11 , I Garcia-Martinez  13   14 , S D Gordon  28 , J M Harris  16 , C A Hartman  29 , A K Henders  28 , A C Heath  30 , I B Hickie  31 , M Hickman  21 , C J Hopfer  32 , J J Hottenga  3 , A C Huizink  5 , D E Irons  9 , R S Kahn  8 , T Korhonen  10   33   34 , H R Kranzler  35 , K Krauter  36 , P A C van Lier  5 , G H Lubke  3   37 , P A F Madden  30 , R Mägi  11 , M K McGue  9 , S E Medland  28 , W H J Meeus  24   38 , M B Miller  9 , G W Montgomery  28 , M G Nivard  3 , I M Nolte  12 , A J Oldehinkel  39 , Z Pausova  6   40 , B Qaiser  10 , L Quaye  16 , J A Ramos-Quiroga  14   15   27 , V Richarte  14 , R J Rose  41 , J Shin  6 , M C Stallings  42 , A I Stiby  21 , T L Wall  43 , M J Wright  28 , H M Koot  5 , T Paus  44   45   46 , J K Hewitt  42 , M Ribasés  13   14   15 , J Kaprio  10   34   47 , M P Boks  8 , H Snieder  12 , T Spector  16 , M R Munafò  21   48 , A Metspalu  11 , J Gelernter  49 , D I Boomsma  3   4 , W G Iacono  9 , N G Martin  28 , N A Gillespie  23   28 , E M Derks  2 , J M Vink  3   50
Affiliations
Meta-Analysis

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

S Stringer et al. Transl Psychiatry. .

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 Disclaimer

Figures

Figure 1
Figure 1
The Manhattan (a) and the QQ plot (b) based on results of the gene-based analysis performed in the discovery sample using HYST (hybrid set-based test).
Figure 2
Figure 2
Forest plot for the top-SNP rs4471463 in the NCAM1 gene on chromosome 11. SNP, single-nucleotide polymorphism.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. United Nations Office on Drugs and Crime. 2010 World Drug Report, New York, USA, 2010.
    1. Hall W, Solowij N. Adverse effects of cannabis. Lancet 1998; 352: 1611–1616. - PubMed
    1. Hall W, Babor TF. Cannabis use and public health: assessing the burden. Addiction 2000; 95: 485–490. - PubMed
    1. Aggarwal SK, Carter GT, Sullivan MD, ZumBrunnen C, Morrill R, Mayer JD. Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. J Opioid Manag 2009; 5: 153–168. - PubMed
    1. Hall W. What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? Addiction 2014; 110: 19–35. - PubMed

Publication types

Grants and funding