Genome-wide association studies (GWAS) have robustly identified the genes DGKH, CACNA1C, and ANK3 novel susceptibility genes for bipolar disorder (BD). DGKH encodes diacylglycerol kinase eta, a key protein in the lithium-sensitive phosphatidyl inositol pathway. The CACNA1C gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. The ANK3 gene encodes ankyrin-G, a large protein whose neural-specific isoforms may help maintain ion channels and cell adhesion molecules.

GWAS in BD have taught us the following important lessons: 1) BD is a polygenic disorder polygenic disorder. The contribution of each locus to risk of disease is modest and disease risk increases substantially with the total burden of risk alleles carried. 2) The best findings from GWAS do not necessarily fall within those genes that have previously been widely studied. 3) Pursuing a "top-hits-only" strategy may prevent us from understanding the genetic complexity of BD and polygenic disorders in general. A detailed consideration of the wider distribution of association signals across studies may prove to be a valuable strategy in complex genetics.4) Allelic heterogeneity may be an important factor in psychiatric disorders. Allelic heterogeneity means that a phenotype can be caused by different alleles within a gene; this phenomenon has been extensively observed in monogenic disorders such as cystic fibrosis as well as in BRCA1/2-associated breast cancer. 5) Finally, as with other complex phenotypes, GWAS in psychiatric disorders demonstrate that the variants identified so far only account for a small fraction of genetic variability.

Future research will need to embark on several complementary approaches in order to fill the yet "unexplained" part of the variance. This will include in-depth sequencing approaches, the search for rare genetic variants such as copy number variations, sophisticated genotype-phenotype dissection approaches, as well as pharmacogenetic studies. Regarding the latter aspect, the work of the Consortium on Lithium Genetics (http://www.ConLigen.org) will be presented.