CONTEXT: We can improve understanding of human methamphetamine dependence, and possibly our abilities to prevent and treat this devastating disorder, by identifying genes whose allelic variants predispose to methamphetamine dependence. OBJECTIVE: To find "methamphetamine dependence" genes identified by each of 2 genome-wide association (GWA) studies of independent samples of methamphetamine-dependent individuals and matched controls. DESIGN: Replicated GWA results in each of 2 case-control studies. SETTING: Japan and Taiwan. PARTICIPANTS: Individuals with methamphetamine dependence and matched control subjects free from psychiatric, substance abuse, or substance dependence diagnoses (N = 580). MAIN OUTCOME MEASURES: "Methamphetamine dependence" genes that were reproducibly identified by clusters of nominally positive single-nucleotide polymorphisms (SNPs) in both samples in ways that were unlikely to represent chance observations, based on Monte Carlo simulations that corrected for multiple comparisons, and subsets of "methamphetamine dependence" genes that were also identified by GWA studies of dependence on other addictive substances, success in quitting smoking, and memory. RESULTS: Genes identified by clustered nominally positive SNPs from both samples were unlikely to represent chance observations (Monte Carlo P < .00001). Variants in these "methamphetamine dependence" genes are likely to alter cell adhesion, enzymatic functions, transcription, cell structure, and DNA, RNA, and/or protein handling or modification. Cell adhesion genes CSMD1 and CDH13 displayed the largest numbers of clustered nominally positive SNPs. "Methamphetamine dependence" genes overlapped, to extents much greater than chance, with genes identified in GWA studies of dependence on other addictive substances, success in quitting smoking, and memory (Monte Carlo P range < .04 to < .00001). CONCLUSION: These data support polygenic contributions to methamphetamine dependence from genes that include those whose variants contribute to dependence on several addictive substances, success in quitting smoking, and mnemonic processes.
CONTEXT: We can improve understanding of humanmethamphetamine dependence, and possibly our abilities to prevent and treat this devastating disorder, by identifying genes whose allelic variants predispose to methamphetamine dependence. OBJECTIVE: To find "methamphetamine dependence" genes identified by each of 2 genome-wide association (GWA) studies of independent samples of methamphetamine-dependent individuals and matched controls. DESIGN: Replicated GWA results in each of 2 case-control studies. SETTING: Japan and Taiwan. PARTICIPANTS: Individuals with methamphetamine dependence and matched control subjects free from psychiatric, substance abuse, or substance dependence diagnoses (N = 580). MAIN OUTCOME MEASURES: "Methamphetamine dependence" genes that were reproducibly identified by clusters of nominally positive single-nucleotide polymorphisms (SNPs) in both samples in ways that were unlikely to represent chance observations, based on Monte Carlo simulations that corrected for multiple comparisons, and subsets of "methamphetamine dependence" genes that were also identified by GWA studies of dependence on other addictive substances, success in quitting smoking, and memory. RESULTS: Genes identified by clustered nominally positive SNPs from both samples were unlikely to represent chance observations (Monte Carlo P < .00001). Variants in these "methamphetamine dependence" genes are likely to alter cell adhesion, enzymatic functions, transcription, cell structure, and DNA, RNA, and/or protein handling or modification. Cell adhesion genes CSMD1 and CDH13 displayed the largest numbers of clustered nominally positive SNPs. "Methamphetamine dependence" genes overlapped, to extents much greater than chance, with genes identified in GWA studies of dependence on other addictive substances, success in quitting smoking, and memory (Monte Carlo P range < .04 to < .00001). CONCLUSION: These data support polygenic contributions to methamphetamine dependence from genes that include those whose variants contribute to dependence on several addictive substances, success in quitting smoking, and mnemonic processes.
Authors: George R Uhl; Tomas Drgon; Catherine Johnson; Marco F Ramoni; Frederique M Behm; Jed E Rose Journal: Mol Med Date: 2010-08-24 Impact factor: 6.354
Authors: Benjamin M Neale; Sarah Medland; Stephan Ripke; Richard J L Anney; Philip Asherson; Jan Buitelaar; Barbara Franke; Michael Gill; Lindsey Kent; Peter Holmans; Frank Middleton; Anita Thapar; Klaus-Peter Lesch; Stephen V Faraone; Mark Daly; Thuy Trang Nguyen; Helmut Schäfer; Hans-Christoph Steinhausen; Andreas Reif; Tobias J Renner; Marcel Romanos; Jasmin Romanos; Andreas Warnke; Susanne Walitza; Christine Freitag; Jobst Meyer; Haukur Palmason; Aribert Rothenberger; Ziarih Hawi; Joseph Sergeant; Herbert Roeyers; Eric Mick; Joseph Biederman Journal: J Am Acad Child Adolesc Psychiatry Date: 2010-08-05 Impact factor: 8.829
Authors: Chunyu Liu; David Saffen; Thomas G Schulze; Margit Burmeister; Pak Chung Sham; Yong-Gang Yao; Po-Hsiu Kuo; Chao Chen; Yu An; Jiapei Dai; Weihua Yue; Miao Xin Li; Hong Xue; Bing Su; Li Chen; Yongyong Shi; Mingqi Qiao; Tiebang Liu; Kun Xia; Raymond C K Chan Journal: Mol Psychiatry Date: 2015-10-20 Impact factor: 15.992
Authors: Tomas Drgon; Ivan Montoya; Catherine Johnson; Qing-Rong Liu; Donna Walther; Dean Hamer; George R Uhl Journal: Mol Med Date: 2008-10-02 Impact factor: 6.354
Authors: Chad A Bousman; Stephen J Glatt; Mariana Cherner; J Hampton Atkinson; Igor Grant; Ming T Tsuang; Ian P Everall Journal: Psychiatry Res Date: 2010-05-15 Impact factor: 3.222
Authors: John K Belknap; Shannon McWeeney; Cheryl Reed; Sue Burkhart-Kasch; Carrie S McKinnon; Na Li; Harue Baba; Angela C Scibelli; Robert Hitzemann; Tamara J Phillips Journal: Mamm Genome Date: 2013-11-13 Impact factor: 2.957
Authors: Jana Drgonova; Donna Walther; G Luke Hartstein; Mohammad O Bukhari; Michael H Baumann; Jonathan Katz; Frank Scott Hall; Elizabeth R Arnold; Shaun Flax; Anthony Riley; Olga Rivero-Martin; Klaus-Peter Lesch; Juan Troncoso; Barbara Ranscht; George R Uhl Journal: Mol Med Date: 2016-08-18 Impact factor: 6.354
Authors: George R Uhl; Tomas Drgon; Catherine Johnson; Chuan-Yun Li; Carlo Contoreggi; Judith Hess; Daniel Naiman; Qing-Rong Liu Journal: Ann N Y Acad Sci Date: 2008-10 Impact factor: 5.691
Authors: Kaixin Zhou; Astrid Dempfle; Mauricio Arcos-Burgos; Steven C Bakker; Tobias Banaschewski; Joseph Biederman; Jan Buitelaar; F Xavier Castellanos; Alysa Doyle; Richard P Ebstein; Jenny Ekholm; Paola Forabosco; Barbara Franke; Christine Freitag; Susann Friedel; Michael Gill; Johannes Hebebrand; Anke Hinney; Christian Jacob; Klaus Peter Lesch; Sandra K Loo; Francisco Lopera; James T McCracken; James J McGough; Jobst Meyer; Eric Mick; Ana Miranda; Maximilian Muenke; Fernando Mulas; Stanley F Nelson; T Trang Nguyen; Robert D Oades; Matthew N Ogdie; Juan David Palacio; David Pineda; Andreas Reif; Tobias J Renner; Herbert Roeyers; Marcel Romanos; Aribert Rothenberger; Helmut Schäfer; Joseph Sergeant; Richard J Sinke; Susan L Smalley; Edmund Sonuga-Barke; Hans-Christoph Steinhausen; Emma van der Meulen; Susanne Walitza; Andreas Warnke; Cathryn M Lewis; Stephen V Faraone; Philip Asherson Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2008-12-05 Impact factor: 3.568