Bipolar Disorder

Bipolar disease (manic-depressive illness, BD) is a common mental disorder with a lifetime prevalence rate of 1%, and is one of the ten major causes of disability worldwide. Epidemiologic data implies that multiple genes and environmental factors play interacting roles in the development of bipolar. Neurogenesis and plasticity are implicated in bipolar disease. But most of the genes in the neurogenesis and plasticity system were not tested for association with BD so far. I propose to perform a systematic association test and resequencing on 35 candidate genes in this system, using -600 Single Nucleotide Polymorphisms (SNPs) in 1540 case-control bipolar samples, to determine if individual gene or multiple genes in the system confer susceptibility to BD.
The combination of very dense genotyping, re-sequencing, and statistical and genomic analyses in this cohort affords an outstanding opportunity to test the neurogenesis and plasticity hypothesis in BD, and to identify gene variants that contribute to BO susceptibility. It is our expectation that we will identify one or several valid associations with candidate genes. An understanding of the role of the associated genes and their pathways in BD susceptibility would reasonably be expected to lead to biologically-based diagnostic categories, improved prediction of susceptibility, and new molecular treatment targets.
Meanwhile, since neurogenesis and plasticity are also hypothesized in other neuropsychiatric illnesses, such as Schizophrenia, Alzheimer’s disease, and others, another important benefit of this work would be the application to those diseases. Informatics development, novel common SNPs and other variants discovered in the resequencing part of this proposal, and fine LD maps around the candidate genes derived from this project, will also be valuable for association studies in many other diseases.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…