THE GENETICS OF BIPOLAR DISORDER
Highlights of a lecture by Ann E. Pulver, Sc.D.
Epidemiologist, Johns Hopkins School of Medicine
Wednesday, February 9, 2000

Dr. Pulver came to MDDA-Boston to discuss the role of genetics in bipolar disorder and to solicit participation in epidemiological studies related to bipolar disorder that are currently underway at Johns Hopkins School of Medicine. Current activities at Johns Hopkins are focused on identifying the genetic basis of bipolar disorder and schizophrenia in hope that this will lead to development of new medications and treatments as well as reduced stigma.

The Role of Genes

Dr. Pulver pointed out that our genes hold all of our hereditary information and provide the “genetic code” that allows our bodies to function, but our environment can affect how our genes function. Half of our genes are inherited from our mothers and half from our fathers.

When looking at genes in the context of bipolar disorder, Dr. Pulver emphasized that genes may confer risk to certain symptoms rather than the disorder itself. For example, with bipolar disorder they look at susceptibility to mania or depression rather than mood disorders as a whole.

Evidence for Role of Genetics in Bipolar Disorder

Population studies, twin studies, and adoption studies were all reviewed for their findings regarding the role of genetics in bipolar disorder. The higher rates of bipolar disorder among relatives, identical twins, and biological parents relative to adoptive parents were all cited as evidence of the role of genetics. These higher risks compare to bipolar disorder occurring in roughly one percent of the population as a whole.

In population studies they found that there is a 10 percent risk that others in the nuclear family (father, mother, siblings) will have the disorder once one family member is diagnosed. Second degree relatives, such as grandparents, uncles, and aunts were found to have a four percent risk.

Twin studies looked at the question of when one twin has bipolar disorder, how often does the other twin also have the disorder? With identical (monozygotic) twins, this was found to be true 60 percent of the time. With fraternal (dizygotic) twins, the frequency was found to be 10 percent, the same as that for traditional siblings.

Adoption studies compared the rate of bipolar disorder in biological and adoptive parents of adoptees with bipolar disorder. Biological parents share the genes of the afflicted person, while the adoptive parents share the same environment. The incidence of bipolar in the biological parents of adoptees with bipolar disorder was 18 percent, while the rate of concurring bipolar disorder in adoptive parents was roughly 7 percent.

Zeroing In On The Risk Areas

Analysis of genetic links to bipolar disorder employs both linkage and association studies. Linkage is a genetic mapping technique that identifies regions of chromosomes that are likely to contain a risk gene. They also rule out chromosome areas where there is a low chance of finding a risk gene. Association studies, on the other hand, require a pretty good idea of where the gene may be located.

Research to date is proving out the relationship between bipolar disorders and schizophrenia as far as their genetic mapping is concerned. A combination of studies have zeroed in on chromosomes 13q, 18p, and 22q as risk genes for bipolar disorder, while 13q, 8p, 22q, 10p, and 6q have been isolated as risk areas for schizophrenia.

Genes Don’t Explain It All

After presenting the compelling genetic evidence, Dr. Pulver emphasized that genetic factors alone do not determine susceptibility to bipolar disorder. The risk for bipolar disorder stems from a complex mix of both genetic and environmental factors, and their current theory is that most individuals who develop these conditions must have several risk genes and significant environmental influences. Dr. Pulver also pointed out that the current line of thought is that bipolar disorder represents not a single gene disorder, but a complex issue involving multiple genes.

The Johns Hopkins Family Studies & The Ashkenazi Jewish Population

The original Johns Hopkins Family Studies on schizophrenia was expanded to include bipolar disorder due to the overlapping clinical features between the two disorders and the hypothesis that susceptibility to both disorders has been linked to the same chromosomal region. Genetic studies benefit from a relatively homogenous gene pool, which is why the Johns Hopkins studies are focusing on the Ashkenazi Jewish population. The ancestors of Ashkenazi Jews come from Eastern Europe or Russia, which represents the majority of the Jewish population in the United States. This population has a long history of marriage within the faith that results in a genetically isolated population with common ancestors.

Study Seeks Participants

Dr. Pulver is currently seeking participants from the Askenazi Jewish population to participate in the John Hopkins studies related to genetics and bipolar disorder. People with the illness will be asked to complete a 3 hour confidential interview and blood draw. If possible, parents and any affected siblings will be asked to participate in a brief phone interview and blood draw.

Jewish people with bipolar disorder who are interested in participating in the study can reach Dr. Pulver at (888) 289-4095 or via email at familystudy@jhmi.edu .

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