Suggestive linkage to chromosomal regions 13q31 and 22q12 in families with psychotic bipolar disorder.
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.
Potash
James B
JB
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, USA. jpotash@jhmi.edu
Zandi
Peter P
PP
Willour
Virginia L
VL
Lan
Tsuo-Hung
TH
Huo
Yuqing
Y
Avramopoulos
Dimitrios
D
Shugart
Yin Y
YY
MacKinnon
Dean F
DF
Simpson
Sylvia G
SG
McMahon
Francis J
FJ
DePaulo
J Raymond
JR
McInnis
Melvin G
MG
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
D005819:Genetic Markers