title: Genetic variants on 3q21 and in the Sp8 transcription factor gene (SP8) as susceptibility loci for psychotic disorders: a genetic association study.
abstract: BACKGROUND
  Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.
  
  
  METHODS
  Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.
  
  
  RESULTS
  Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10(-8)) only for BD (P = 9.4×10(-9)) and psychosis (P = 2.0×10(-10)). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10(-7) for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10(-3)).
  
  
  CONCLUSIONS
  We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.
authors: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors: Kenji
authors: K
authors: Kondo
authors: Masashi
authors: M
authors: Ikeda
authors: Yusuke
authors: Y
authors: Kajio
authors: Takeo
authors: T
authors: Saito
authors: Yoshimi
authors: Y
authors: Iwayama
authors: Branko
authors: B
authors: Aleksic
authors: Kazuo
authors: K
authors: Yamada
authors: Tomoko
authors: T
authors: Toyota
authors: Eiji
authors: E
authors: Hattori
authors: Hiroshi
authors: H
authors: Ujike
authors: Toshiya
authors: T
authors: Inada
authors: Hiroshi
authors: H
authors: Kunugi
authors: Tadafumi
authors: T
authors: Kato
authors: Takeo
authors: T
authors: Yoshikawa
authors: Norio
authors: N
authors: Ozaki
authors: Nakao
authors: N
authors: Iwata
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics*; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C501901:SP8 protein, human
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