10 May 2016
May 11, 2016. Schizophrenia's genetic roots appear to lie not so much in damaged proteins, but rather in perturbations to when and how often genes are turned on to make their proteins. The common genetic variants associated with schizophrenia risk are spread across more than 100 locations in the genome, and more often than not, these risk variants occur in regions of the genome that instruct cells on when and how much protein to produce, or "express," from the gene blueprint.
Two new studies support this view by finding evidence of an altered gene expression program in schizophrenia. Looking at the patterns of methyl groups added on top of DNA, which leaves genes in a "dormant" state, the researchers pinpointed methylation differences between schizophrenia and controls. Together, the studies underline the importance of the epigenome—the various chemical groups added to DNA, of which methylation is only one—to understanding schizophrenia's roots.
The first study, published in JAMA Psychiatry on May 1, surveyed the gene-suppressing methylation marks on DNA obtained from blood samples from nearly 2,000 people, and identified 172 sites associated with schizophrenia. Future work will determine how much of this also occurs in the brain, since the epigenetic landscape of brain cells will differ somewhat from blood cells. Yet the blood-based approach could lead to biomarkers that might reflect some of a person's risk for schizophrenia.
"What we and many others are trying to understand is, How much of a useful glimpse can you get if you look at blood, given that this is the feasibly accessible tissue?" said Daniele Fallin who co-led the methylation association study with Andrew Feinberg, both at Johns Hopkins University in Baltimore, Maryland.
The second study, published online in the American Journal of Human Genetics on April 13, examined DNA extracted from postmortem brain samples. Led by Art Petronis of the University of Toronto, Canada, the study found that certain variants in the genome were associated with methylation atop nearby DNA. The study suggested that genetic factors contributing to schizophrenia may well do so by influencing methylation and, in turn, levels of gene expression. (For more details, see the related news story.)—Michele Solis.