People with bipolar disorder suffer from alternating episodes of mania--uncontrolled exuberance--and depression. Studies have clearly established a role of heredity in bipolar disorder. Most scientists believe that many genes, each with a small effect, act together to cause bipolar disorder, a scenario that makes it difficult to pinpoint the responsible genes. However, the advent of genome-wide association studies has identified some strong candidates.
Family Studies
In their review of the genetics of bipolar disorder in the November 2009 issue of Neuroscience, Drs. Barnett and Smoller cite studies showing that if one member of a family has bipolar disorder, their siblings, parents and children have 10 times greater risk of having bipolar disorder compared to someone in the general population. Their relatives are also three times more likely to have major depression. Barnett and Smoller cite evidence that heritability of bipolar disorder, meaning the risk for bipolar disorder that comes from genetic causes, ranges from 73 to 93 percent, even higher than the heritability of breast cancer.
Twin Studies
According to a study cited in Online Mendelian Inheritance in Man, scientists found that in 54 percent of cases in which one identical twin has bipolar disorder, the other twin also has the disorder. Scientists refer to this phenomenon as concordance. In contrast to identical twins, fraternal twins show only 14 percent concordance for bipolar disorder. Because identical twins have all of the same genes, while fraternal twins share no more than 50 percent of their genes on average, this is strong evidence for a genetic component to bipolar disorder. Barnett and Smoller assert that this makes bipolar disorder one of the most heritable of all medical disorders. However, if bipolar disorder arose solely from genetic causes, concordance in identical twins would be close to 100 percent, so this data also suggests that there is a strong environmental component to bipolar disorder.
Genome-Wide Association Studies
Genome-wide association studies survey every human gene for changes that appear in people with a disease at a significantly different frequency than in people without the disease. One such study sponsored by the National Institute of Mental Health reported associations between genes that control nerve cell function and the likelihood of having bipolar disorder. These genes, ANK3 and CACNA1C, encode proteins that control the flow of sodium and calcium into nerve cells to regulate brain activity. As reported by Barnett, the bipolar medication lithium acts to reduce the levels of both ANK3 and CACNA1C expression in the brain, strongly implicating these gene as contributors to bipolar disorder. Barnett’s review also cites a separate genome-wide association study that showed strong evidence for a role of the PALB2 gene in bipolar disorder. The PALB2 gene product helps stabilize the DNA structure of other genes, controlling their expression, but it is not clear how this contributes to bipolar disorder.
References
- “Neuroscience”; The Genetics of Bipolar Disorder; J.H. Barnett and J.W. Smoller; November 2009
- Online Mendelian Inheritance in Man: Major Affective Disorder 1
