A study suggesting that bipolar disorder may be a polygenic disorder is to be published online in the journal Molecular Psychiatry. This first genome-wide association study of bipolar disorder has implications for the way future studies should approach research into the genetics of the condition.
Bipolar disorder, also known as manic-depression, is a psychiatric condition defined by periods of extreme mood. One in every 100 individuals is diagnosed as having bipolar disorder and they have a high risk of becoming suicidal. Francis J. McMahon and colleagues carried out a study using pooled DNA from two independent case-control samples of European ancestry. The case sample consisted of unrelated individuals selected from families with at least one affected sibling pair, while the control sample consisted of individuals who did not meet criteria for major depression and denied a history of bipolar disorder or psychosis. Over 550,000 single-nucleotide polymorphisms (SNPs) were used to measure the genetic variation between the samples. SNPs that occurred more often in the people with bipolar disorder were examined individually. No one gene appears to be necessary or sufficient for disease. Instead, several genes, each of modest effect, were shown to contribute to the risk of bipolar disorder - with each person's disease risk being influenced by the total burden of risk alleles they carry. Several of the implicated genes lie within regions previously linked to Schizophrenia.
One of the identified genes, DGKH, did stand out for having the strongest result in the study. DGKH encodes diacylglycerol kinase eta, a key protein in the lithium-sensitive phosphatidyl inositol pathway. The phosphatidyl inositol pathway has been hypothesized to play a role in the mechanism of action of mood-stabilizing medications.
Francis J. McMahon (National Institute of Mental Health, NIH, Bethesda, MD, USA)
Ogechi Okoli (Nature Publishing Group, London)
Abstract available online.
(C) Molecular Psychiatry press release.
Message posted by: Trevor M. D'Souza