UCLA. US: Common psychiatric disorders such as schizophrenia, bipolar disorder
and major depression share genetic risk factors related to immune
function and DNA regulation, according to new findings by a large
collaborative research project from the Psychiatric Genomics Consortium
involving UCLA, King’s College London, Cardiff University, Harvard and
MIT.
The study was published online by the journal Nature Neuroscience.
Thousands of genetic differences in the human genome act together to
increase the risk for psychiatric conditions such as schizophrenia.
However, until now, it has not been clear how these genetic changes
affect biological processes that then go on to alter brain function.
In the study the group analyzed genetic data from more than 60,000
participants, including individuals with schizophrenia, bipolar
disorder, major depression, autism spectrum disorders and attention
deficit hyperactivity disorder, as well as healthy individuals. The aim
was to identify which biological and biochemical pathways caused risk
for these disorders.
By grouping the genetic data together, the consortium found that
genes relating to immune function and histone methylation — molecular
changes that alter DNA expression — are risk factors associated with the
development of all the disorders. Such biological pathways are
important, they noted, because they are much broader drug targets than
single genes or proteins.
“We took the hundreds of genes in the biological pathways identified
by our collaborators and modeled them as a gene network,” said Daniel
Geschwind, a UCLA professor of neurology, psychiatry, and genetics, and a
study author.
This approach allowed the researchers to explore the role of these
pathways during brain development and aging. Geschwind said that this
further enhanced their ability to detect shared biology across these
diseases and identifies the points in time and regions of the brain that
are most susceptible.
“The success of this approach supports the utility of pathway and
network analyses in understanding psychiatric disease,” said Geschwind,
who is also director of the Center for Autism Research and Treatment at the UCLA Semel Institute.
“This is an approach that will only grow more powerful as more loci are
identified with even larger studies in the next few years.”
The study is the result of many years of work by hundreds of investigators worldwide in the Psychiatric Genomics Consortium,
an international, multi-institutional collaboration founded in 2007 to
conduct broad-scale analyses of genetic data for psychiatric disease.
The PGC is currently genotyping new samples to further study these and
additional psychiatric diseases, including anorexia and post-traumatic
stress disorder.
Core funding for the Psychiatric Genomics Consortium comes from the
National Institute of Mental Health, along with grants from governmental
and charitable organizations, as well as philanthropic donations. Work
conducted at King’s College London was funded by the National Institute
for Health Research Biomedical Research Centre and Dementia Unit at
King’s and South London and Maudsley, the NHS Foundation Trust and
Cardiff by the MRC and the Wellcome Trust. Work at the Broad Institute’s
Stanley Center for Psychiatric Research was funded by Sylvan Herman
Foundation and the Stanley Medical Research Institute.