GAD1 single nucleotide polymorphism is in linkage disequilibrium with a child bipolar I disorder phenotype.
BACKGROUND
Pediatric bipolar I disorder (BP-I) and childhood schizophrenia (SZ) share certain symptoms (e.g., psychosis, aggression/irritability [A/I]), and the psychotic and A/I features are treated with neuroleptics in both disorders. Thus, it is of interest to examine the association of GAD1 to child BP-I because of its recently reported association to childhood SZ.


METHODS
Child BP-I probands were obtained by consecutive new case ascertainment, and the phenotype was defined as current DSM-IV BP-I (manic or mixed phase) with at least one of the cardinal symptoms of mania (i.e., elation and/or grandiosity) and a Children's Global Assessment Scale score < or =60 (clinical impairment). These child BP-I probands are part of a large, ongoing, longitudinal study in which the phenotype has been validated by unique symptoms, longitudinal stability, and 7-8 times greater family loading than adult BP-I probands. Genotyping was performed using a TaqMan Validated SNP Genotyping Assay, and FBAT was used for analysis.


RESULTS
There were 48 families. The rs2241165 A allele was preferentially transmitted (FBAT chi(2) = 5.2, df = 1, p = 0.022). No interaction between this GAD1 SNP and the Val66 BDNF allele was found.


CONCLUSIONS
These data are consistent with some shared genetic vulnerability between child BP-I and SZ, which may be related to similar treatments.
Geller
Barbara
B
Department of Psychiatry, Washington University in St. Louis, 660 South Euclid Avenue, St. Louis, MO 63110, USA. gellerb@medicine.wustl.edu
Tillman
Rebecca
R
Bolhofner
Kristine
K
Hennessy
Kathleen
K
Cook
Edwin H
EH
D000293:Adolescent; D001714:Bipolar Disorder / Q000235:genetics*; D002648:Child; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1