Genome-wide association for methamphetamine dependence: convergent results from 2 samples.
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.
Uhl
George R
GR
Molecular Neurobiology Branch, National Institutes of Health Intramural Program, Department of Health and Human Services, Baltimore, Maryland 21224, USA. guhl@intra.nida.nih.gov
Drgon
Tomas
T
Liu
Qing-Rong
QR
Johnson
Catherine
C
Walther
Donna
D
Komiyama
Tokutaro
T
Harano
Mutsuo
M
Sekine
Yoshimoto
Y
Inada
Toshiya
T
Ozaki
Norio
N
Iyo
Masaomi
M
Iwata
Nakao
N
Yamada
Mitsuhiko
M
Sora
Ichiro
I
Chen
Chih-Ken
CK
Liu
Hsing-Cheng
HC
Ujike
Hiroshi
H
Lin
Shih-Ku
SK
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
C477880:CSMD1 protein, human; D015820:Cadherins; C099972:H-cadherin; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D008694:Methamphetamine