title: Suggestive linkage to chromosomal regions 13q31 and 22q12 in families with psychotic bipolar disorder.
abstract: OBJECTIVE
  Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions-10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms-defined as hallucinations and/or delusions-in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap.
  
  
  METHODS
  Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder.
  
  
  RESULTS
  The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings.
  
  
  CONCLUSIONS
  Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, USA. jpotash@jhmi.edu
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Willour
authors.forename: Tsuo-Hung
authors.initials: TH
authors.lastname: Lan
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Avramopoulos
authors.forename: Yin Y
authors.initials: YY
authors.lastname: Shugart
authors.forename: Dean F
authors.initials: DF
authors.lastname: MacKinnon
authors.forename: Sylvia G
authors.initials: SG
authors.lastname: Simpson
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: J Raymond
authors.initials: JR
authors.lastname: DePaulo
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
mesh_terms: D000341:Affective Disorders, Psychotic / Q000453:epidemiology / Q000235:genetics; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D016000:Cluster Analysis; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015995:Prevalence; D012559:Schizophrenia / Q000235:genetics
chemical_list: D005819:Genetic Markers