Genetics of Bipolar Disorder

Fifty percent of patients with bipolar disorder have a family history. In families known as multiplex families, the majority of members display the phenotype of the disorder across generations. Twin studies show that the concordance for bipolar illness is between 40 percent and 80 percent in monozygotic twins and is only 10 to 20 percent in dizygotic twins, which suggests a genetic component to the disorder. No Mendelian pattern has been discovered yet, but statistical analyses have computed patterns of polygenic inheritance.

Bipolar disorder occurs in a high incidence in the Old Order Amish community. This community is descended from a small number of immigrants who settled in Lancaster, Pennsylvania before 1750. The  community kept excellent genealogical, disease, and death records. This allowed researchers to study the chromosomes of hundreds of affected individuals and identify the specific gene (a missense variant of KCNH7) responsible for bipolar disorder in the Old Order Amish (Egeland, 1988). However, more than one gene may be  responsible for a disorder and epigenetic factors may make it difficult to ascertain the specific function of each gene. In fact, subsequent research indicated that multiple genes contribute to risk for bipolar disorder in the Old Order Amish (Georgi et al., 2014). Moreover, in the general population, bipolar disorder has been shown to be affected by multiple genes (polygenic) and affected by environmental factors (Serretti & Mandelli, 2008).

Genomewide association analysis, which identifies susceptibility genes for complex disorders, has begun to implicate specific genes for bipolar disorder, namely DGKH, CACNA1C, and ANK3. Since bipolar disorder is polygenic, large samples are necessary to find the modest effect loci that are factors in bipolar disorder (Barnett & Smoller, 2009).

Barnett, J. H., & Smoller, J. W. (2009). The genetics of bipolar disorder. Neuroscience, 164(1), 331-343.

Egeland, J. (1988). A Genetic Study of Manic-depressive Disorder among the Old Order Amish of Pennsylvania. Pharmacopsychiatry, 21(02), 74–75. doi: 10.1055/s-2007-1014651 

Georgi, B., Craig, D., Kember, R. L., Liu, W., Lindquist, I., Nasser, S., … Bućan, M. (2014). Genomic View of Bipolar Disorder Revealed by Whole Genome Sequencing in a Genetic Isolate. PLoS Genetics, 10(3). doi: 10.1371/journal.pgen.1004229

Serretti, A. & Mandelli, L. (2008) The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions. Mol Psychiatry 13, 742–771 doi:10.1038/mp.2008.29