title: Genome-wide association for methamphetamine dependence: convergent results from 2 samples.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Replicated GWA results in each of 2 case-control studies.
  
  
  METHODS
  Japan and Taiwan.
  
  
  METHODS
  Individuals with methamphetamine dependence and matched control subjects free from psychiatric, substance abuse, or substance dependence diagnoses (N = 580).
  
  
  METHODS
  "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).
  
  
  CONCLUSIONS
  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.affiliation: Molecular Neurobiology Branch, National Institutes of Health Intramural Program, Department of Health and Human Services, Baltimore, Maryland 21224, USA. guhl@intra.nida.nih.gov
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Tomas
authors.initials: T
authors.lastname: Drgon
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
authors.forename: Catherine
authors.initials: C
authors.lastname: Johnson
authors.forename: Donna
authors.initials: D
authors.lastname: Walther
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Chih-Ken
authors.initials: CK
authors.lastname: Chen
authors.forename: Hsing-Cheng
authors.initials: HC
authors.lastname: Liu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Shih-Ku
authors.initials: SK
authors.lastname: Lin
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D016678:Genome; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008694:Methamphetamine; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins
chemical_list: C477880:CSMD1 protein, human; D015820:Cadherins; C099972:H-cadherin; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D008694:Methamphetamine