title: DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort.
abstract: BACKGROUND
  Genetic evidence implicates the DISC1 gene in the etiology of a number of mental illnesses. Previously, we have reported association between DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome-wide association analysis has recently been performed.
  
  
  METHODS
  In the present study, we re-analyzed the genome-wide association data with regard to these two measures of psychosis proneness, conditioning on our previous DISC1 observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals provided phenotype and genotype data. No markers were significant at the genome-wide level. However, several genes with biological relevance to mental illnesses were highlighted through loci displaying suggestive evidence for association (≥3 SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT, MED13L, TMCO7, TTN, and the micro RNA MIR620.
  
  
  CONCLUSIONS
  By conditioning a previous genome-wide association study on DISC1, we have been able to identify eight genes as associating to psychosis proneness. Further, these molecules predominantly link to the DISC1 pathway, strengthening the evidence for the role of this gene network in the etiology of mental illness. The use of quantitative measures of psychosis proneness in a large population cohort will make these findings, once verified; more generalized to a broad selection of disorders related to psychoses and psychosis proneness.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Tomppo
authors.forename: Jesper
authors.initials: J
authors.lastname: Ekelund
authors.forename: Dirk
authors.initials: D
authors.lastname: Lichtermann
authors.forename: Juha
authors.initials: J
authors.lastname: Veijola
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: William
authors.initials: W
authors.lastname: Hennah
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins