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GAD1 single nucleotide polymorphism is in linkage disequilibrium with a child bipolar I disorder phenotype
Barbara Geller1, Rebecca Tillman, Kristine Bolhofner
1Department of Psychiatry, Washington University in St. Louis, 660 South Euclid Avenue, St. Louis, MO 63110, USA. gellerb@medicine.wustl.edu
Insights
Genetic analysis suggests a shared vulnerability between pediatric bipolar I disorder and childhood schizophrenia. The GAD1 gene
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Pediatric bipolar I disorder (BP-I) and childhood schizophrenia (SZ) share symptoms like psychosis and aggression, treated with neuroleptics.
- GAD1 gene association with childhood SZ warrants investigation in child BP-I due to symptom overlap.
Purpose of the Study:
- To investigate the association of the GAD1 gene with pediatric bipolar I disorder.
- To explore potential shared genetic factors between child BP-I and SZ.
Main Methods:
- Utilized a cohort of 48 child BP-I probands meeting DSM-IV criteria.
- Phenotype defined by manic/mixed phase, cardinal mania symptoms, and clinical impairment (CGAS <= 60).
- Employed TaqMan SNP genotyping and Family-Based Association Test (FBAT) for genetic analysis.
Main Results:
- The rs2241165 A allele of the GAD1 gene was preferentially transmitted in child BP-I families (p = 0.022).
- No significant interaction was observed between the GAD1 SNP and the Val66 BDNF allele.
Conclusions:
- Findings support a potential shared genetic vulnerability between child BP-I and childhood SZ.
- This shared genetic basis may contribute to the similar treatment approaches for both disorders.
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.
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