Abnormal sequences of DNA known as rare copy number variants (CNVs) may play a role in the risk for early-onset bipolar disorder, according to new research from an international team of scientists.
The variants, also known as CNVs, are alterations in which there are too few or too many copies of sections of DNA. Researchers have known that spontaneously occurring or de novo CNVs, which are genetic mutations not inherited from parents, increase the risk for some neuropsychiatric conditions, such as schizophrenia or autism.
But their role was unclear in bipolar disorder, according to principal investigator Jonathan Sebat, Ph.D., assistant professor of psychiatry and cellular and molecular medicine at the University of California San Diego’s Institute of Genomic Medicine.
Sebat and his colleagues found that de novo CNVs contribute “significant” genetic risk in about 5 percent of early-onset bipolar disorder, which appears in childhood or early adulthood.
The cause — or causes — of bipolar disorder remain unclear, noted the study’s first author Dheeraj Malhotra, Ph.D., assistant project scientist in Sebat’s lab.
Researchers know there is a clear genetic component as the disease runs in families, but previous studies that focused on commonly inherited variants have met with limited success in identifying key susceptibility genes, he said.
Malhotra noted that while the findings do not conclusively pinpoint a specific gene or genomic region, they show “convincing” evidence that rare copy number mutations contribute to the development of early onset bipolar disorder.
He added that sequencing of complete genomes or exomes of a large number of bipolar families is needed to determine the genetic contribution of all forms of de novo mutations to the risk for bipolar disorder.
The findings were published in the Dec. 22 issue of the journal Neuron.