Genetics of bipolar disorder.

Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a "risk" allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are currently not fulfilled for common genomic variants in psychiatric disorders. Further work is clearly needed before genetic testing for common variants in psychiatric disorders should be established.