Knowledgebase for Addiction-Related Genes
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KARG (Knowledgebase for Addiction Related Genes) >> Genetics View
Here we report the first comprehensive field synopsis of genetic association studies in drug addiction. We manually curate and integrate 886 candidate gene association studies and 11 GWA studies. Totally 843 vulnerable hyplotypes were identified, linked by 12 risk variants and 842 vulnerable SNPs.
  Systematic meta-analyses of low-scale genetic association studies for drug addiction (See the Full List)

Drug Addiction has become one of the most serious problems in the world. We extracted 506 allelic contrasts tests on 286 genetic variants. For all variants with case-control genotype data available in three or more independent samples, we systematically carried out meta-analyses using both the DerSimonian & Laird random-effects model and fixed-effects model. Across 35 candidate gene meta-analyses, a total of 12 genetic variants in 11 different genes (BDNF, CCK, CNR1, COMT, DRD2, DRD4, FAAH, HNMT, OPRK1, OPRM1, SLC4A7) showed nominally significant effects. Six of these variants can be characterized as showing strong epidemiological credibility, as suggested by the criteria of HuGENet Road Map, which is recently proposed for the assessment of cumulative evidence in genetic association studies. All data are freely available for download at: http://karg.cbi.pku.edu.cn/karg2/ls.php.

  Meta-analyses of Genome-Wide Association Studies (GWAS) (See the Full List)
   Welcome to the KARG 2.0: Knowledgebase for Addiction Related Genes.

We identified 10 GWAS studies focused on drug addiction, with 11 independent samples. 5 of them can meet our inclusion criteria, including i) genetic association studies with case-control design, ii) published in a peer-reviewed scientific journals, iii) published in English and iv) original case-control genotype data available. All these five microarray datasets were downloaded from public web sites or provided by the authors upon request. Initial data analyses were performed and Student¡¯s t tests were conducted to access the vulnerability of each SNP marker, following the protocols published before. We integrated these 11 GWAS datasets using a meta-signature-based approach. 842 SNPs were identified with at least three items of positive evidence and meta-false discovery rate less than 0.05.

Since most of these genetic vulnerable markers are in fact genetic ¡®tag markers¡¯ instead of functional variations, we further expanded this list to 1,907 unique SNPs on the basis of the whole-genome linkage equilibrium data identified by HapMap.

Finally, we integrated all available SNP functions to date and performed a comprehensive annotation to facilitate the interpretation of those addiction vulnerable variants identified by association studies. We identified 124 ¡®functional¡¯ SNPs dropped into 70 hyplotype blocks. These functional SNPs include nonsynonymous/synonymous SNPs, SNPs putatively modifying transcription factor/microRNA binding or processes of alternative splicing, SNPs under positive or negative selections and SNPs with strong correlations with differentially gene expression.

The full list of the GWAS meta-analyses data are available at:

http://karg.cbi.pku.edu.cn/karg2/gwas.php

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  News ¡¡

July 10th, 2010: Release of KARG 2.0 data: Meta-analysis and Genome-wide Interpretation of Genetic Susceptibility to Drug Addiction.

Mar  4th, 2010: On the basis of  KARG data, We identified the first human-specific protein-coding gene that originated through de novo evolution. The work has been accepted by PLoS Computational Biology. (See Links)

Mar  2nd, 2008:  NIDA/NIH (National Institute on Drug Abuse, National Institutes of Health) added a link to KARG on their website. (See Links)

Feb  5th, 2008:  KARG was featured by Science (STKE) as "Editors' Choice": "A Bioinformatics Approach to Addiction". (See Comment)

Jan 10th, 2008:  KARG was commented by The Economist (Both Printed and Online version):

                                       "A group of Chinese scientists has discovered the main biochemical pathways in drug addiction—and without having to do a single experiment". (See Comment)

Jan 25th, 2008:  KARG was commented by Chinese Journal of Science. (See Comment)

Jan 14th, 2008:  KARG was commented by China Daily: "Genes behind drug addiction tracked". (See Comment)

Jan  8th, 2008:  KARG was commented by REUTERS: "Drug addiction genes identified". (See Comment)

Jan  4th, 2008:  The Public Library of Science (PLoS) published a press release to comment on KARG, which was rapidly published by more than 30 websites. "Assembling The Jigsaw Puzzle Of Drug Addiction". (See Comment)

Dec 19th, 2007:  KARG was highlighted by Nature China: "Drug addiction: The ultimate gene list". (See comment)

Jan 4th, 2008:  KARG was published on PLoS Computational Biology:

                                     Li CY, Mao X, Wei L (2008) Genes and (common) pathways underlying drug addiction. PLoS Comput Biol 4(1): e2. doi:10.1371/journal.pcbi.0040002 (PubMed) (Full Text)

Oct 11th, 2007:  KARG was submitted to PLoS Computational Biology.

Jan  1st, 2007:  KARG 1.0 data freeze. a total of 1500 human genes were linked to addiction with 2343 independent evidences.

Nov  1st, 2005: The KARG project launched in Center for Bioinformatics, Peking University.

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  Center for Bioinformatics(CBI), Peking University. Any Comments and suggestions to : KARG GROUP