Related Experiment Video
Updated: Jul 12, 2026
04:42
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Sequence variation in DOCK9 and heterogeneity in bipolar disorder
Sevilla D Detera-Wadleigh1, Chun-yu Liu, Manjula Maheshwari
1Genetic Basis of Mood and Anxiety Disorders, Mood and Anxiety Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health/U.S. DHHS, 35 Convent Drive, Bethesda, MD 20892, USA. deteras@mail.nih.gov
Psychiatric Genetics
|August 31, 2007
Summary
Researchers identified the DOCK9 gene as a potential risk factor for bipolar disorder, influencing both disease susceptibility and severity. This finding implicates the Rho-GTPase pathway in bipolar disorder etiology.
Area of Science:
- Genetics
- Neuroscience
- Psychiatry
Background:
- Bipolar disorder linkage has been associated with chromosome 13q.
- Previous studies identified the DAOA (G72) locus on 13q33, but it may not fully explain the linkage evidence.
- Further investigation is needed to identify additional susceptibility loci in the 13q32-q33 region.
Purpose of the Study:
- To identify additional susceptibility loci on chromosome 13q32-q33 using linkage disequilibrium mapping.
- To explore the impact of phenotypic heterogeneity on genetic association studies of bipolar disorder.
Main Methods:
- Genotyped 98 single nucleotide polymorphisms (SNPs) on 13q32-q33 in 285 bipolar disorder probands and their parents.
- Conducted fine-scale mapping on DOCK9, a gene showing initial association.
- Performed secondary analysis of familial component phenotypes of bipolar disorder.
Main Results:
- Three SNPs in the DOCK9 gene showed significant excess allelic transmission (P=0.0477-0.00067).
- Fine-scale mapping identified nine associated SNPs within DOCK9 (P=0.02-0.006).
- Maternally transmitted alleles of DOCK9 were largely responsible for association signals, and specific DOCK9 markers associated with bipolar disorder phenotypes like psychosis and delusions.
Conclusions:
- DOCK9 is implicated in both the risk and increased severity of bipolar disorder.
- Phenotypic heterogeneity significantly impacts genetic association findings.
- This study is the first to suggest DOCK9 and the Rho-GTPase pathway's role in bipolar disorder etiology.
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