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The Bipolar Disorder workgroup has been a part of the PGC since the beginning of PGC. Our membership has grown to include investigators from more than 200 institutions world-wide.
Our members are clinical and basic science researchers with a wide range of expertise from psychiatry to psychology, human genetics, biostatistics, bioinformatics, cellular modelling and drug discovery.
Bipolar disorder, also known as manic depressive illness, is a mental health condition that affects mood, energy levels, activity, and concentration or focus. The main symptoms of bipolar disorder are episodes of extreme highs, called mania, and lows (depression). These highs and lows are different from the ups and downs we all experience: they are extreme, can last for several weeks, causing significant distress and interfering with daily life. Episodes of illness can occur occasionally and at irregular intervals or be long-lasting. In many cases, bipolar disorder requires lifetime treatment, even when symptoms are not present.
Bipolar disorder increases the risk of suicide by 10-30 times (PMID: 31344941).
The World Health Organisation ranks bipolar disorder as one of the top causes of lost years of life and health in 15 to 44 year olds (PMID: 23993280).
The exact cause of bipolar disorder is unknown, but it is likely that there is no single cause. Instead, a combination of factors may contribute to bipolar disorder. Bipolar disorder runs in families. Research suggests that genetic factors are largely responsible for this familial aggregation and are believed to account for 60–80 percent of the risk of developing the disorder (PMID: 23663951). However, most people who have a close relative with bipolar disorder will not develop any psychiatric disorder and most people with bipolar disorder don’t have any family member affected.
Genetic factors are not the sole determinant of bipolar disorder. Environment does also play a role.
Our most recent study has explored common genetic variations (called single nucleotide polymorphisms, SNPs) in over 29,000 individuals with bipolar disorder and 160,000 controls. We found 30 positions in the DNA sequence that increase the risk of developing the disorder. Our analyses pointed to genes relevant to the nervous, immune and metabolic systems. They implicated genes for ion channels, which help convert chemical and mechanical clues into electrical signals, neurotransmitter transporters and synaptic elements.
We also found differences in the genetic make-up between individuals with bipolar disorder and history of severe manic episodes (often called bipolar I disorder) and those without history of such severe episodes (bipolar II disorder). In our genetic analyses, bipolar I disorder was more strongly correlated with schizophrenia whereas bipolar II disorder was more strongly correlated with major depression.
Our group has also contributed to cross-disorder analyses that explored the genetic overlap with other major psychiatric disorders (PMID: 23933821, PMID: 23453885), including the identification of biological pathways shared by schizophrenia, major depression and bipolar disorder (PMID: 26007216). Together with the Schizophrenia workgroup, we have identified genetic regions that differentiate between the two disorders and examined the effect of schizophrenia genetic risk on the presentation of bipolar disorder and vice versa (PMID: 29906448).
We are currently looking to increase the number of studies with genotype and clinical information on individuals with bipolar disorder, including those from overlooked ancestry groups. By linking genetic and clinical data, we hope to identify different sub-groups of individuals with bipolar disorder with different genetic signatures. Our analyses may provide useful information to develop new, more effective and tailored treatments and improve the management of bipolar disorder or of the risk of developing it.
We have monthly conference calls to discuss the management of the group and regular email contact on a list serve. For our open source commitment and data sharing policy, please read http://www.med.unc.edu/pgc/shared-methods/open-source-philosophy.
If you think you are able to contribute to our workgroup, please contact the chair, Ole Andreassen.
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8.
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. The genetics of the mood disorder spectrum: genome-wide association analyses of more than 185,000 cases and 439,000 controls. Biol Psychiatry. 2019 Nov 1, in press. doi: 10.1016/j.biopsych.2019.10.015.
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell. 2018 Jun 14;173(7):1705-1715.e16. doi: 10.1016/j.cell.2018.05.046.