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Wednesday, July 23, 2014

Schizophrenia's genetic 'skyline' rising as genetic code linked to illness grows

The largest genomic dragnet of any psychiatric disorder to date has unmasked 108 chromosomal sites harboring inherited variations in the genetic code linked to schizophrenia, 83 of which had not been previously reported. By contrast, the 'skyline' of such suspect variants associated with the disorder contained only 5 significant peaks in 2011. Researchers combined data from all available schizophrenia genetic samples to boost statistical power high enough to detect subtle effects on risk.

>>"While the suspect variation identified so far only explains only about 3.5% of the risk for schizophrenia, these results warrant exploring whether using such data to calculate an individual's risk for developing the disorder might someday be useful in screening for preventive interventions," .... "Even based on these early predictors, people who score in the top 10% of risk may be up to 20-fold more prone to developing schizophrenia."
>>The newfound genomic signals are not simply random sites of variation... They converge around pathways underlying the workings of processes involved in the disorder, eg communication between brain cells, learning and memory, cellular ion channels, immune function and a key medication target.
>>There was an association confirmed with variation in the gene that codes for a receptor for dopamine: target for antipsychotic medications used to treat schizophrenia. Yet evidence from the study supports the view that most variants appear to exert their effects via the turning on and off of genes rather than through coding for proteins.
>>The study found a notable overlap between protein-related functions of some linked common variants and rare variants associated with schizophrenia in other studies incl genes in communication between neurons via the chemical messenger glutamate, learning and memory, and the machinery controlling the influx of calcium into cells.
"The overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia,"
>>Findings confirm that it's possible to develop risk profile scores based on schizophrenia-associated variants that may be useful in research - but, for now, aren't sensitive or specific enough to be used clinically as a predictive test, say the researchers.