title: Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia.
abstract: Methamphetamine (METH) use can provoke psychotic reactions requiring immediate treatment, namely METH-induced psychosis. Although the distinction between METH-induced and primary psychosis is important for understanding their clinical courses, we do not have clear diagnostic procedure by their symptoms. Not only are there similarities between the clinical features of METH-induced psychosis and schizophrenia (SCZ), but there is also epidemiological evidence of a shared genetic risk between 'METH-related' disorders and SCZ, which makes the differentiation of these two conditions difficult. In this study, we conducted a genome-wide association study (GWAS) targeting METH-dependent patients. The METH sample group, used in the METH-dependence GWAS, included 236 METH-dependent patients and 864 healthy controls. We also included a 'within-case' comparison between 194 METH-induced psychosis patients and 42 METH-dependent patients without psychosis in a METH-induced psychosis GWAS. To investigate the shared genetic components between METH dependence, METH-induced psychosis, and SCZ, data from our previous SCZ GWAS (total N=1108) were re-analyzed. In the SNP-based analysis, none of the SNPs showed genome-wide significance in either data set. By performing a polygenic component analysis, however, we found that a large number of 'risk' alleles for METH-induced psychosis are over-represented in individuals with SCZ (Pbest=0.0090). Conversely, we did not detect enrichment either between METH dependence and METH-induced psychosis or between METH dependence and SCZ. The results support previous epidemiological and neurobiological evidence for a relationship between METH-induced psychosis and SCZ. These also suggest that the overlap between genes scored as positive in these data sets can have higher probability as susceptibility genes for psychosis.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okahisa
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Mujun
authors.initials: M
authors.lastname: Won
authors.forename: Naoki
authors.initials: N
authors.lastname: Kondo
authors.forename: Nobuya
authors.initials: N
authors.lastname: Naruse
authors.forename: Kumi
authors.initials: K
authors.lastname: Aoyama-Uehara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Taku
authors.initials: T
authors.lastname: Miyagawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000483:Alleles; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011605:Psychoses, Substance-Induced / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D008694:Methamphetamine