Two large, international studies have independently found three genetic mutations that are linked to a greatly increased risk of schizophrenia, but say the rare mutations only account for a small percentage of schizophrenia cases. The identification of the three mutations is being hailed as a breakthrough, as no genetic factors had been definitively linked to the disease before. But in a finding of even greater importance, the studies suggest that there's no easy answer to the question of what causes the devastating mental illness. Instead of a common genetic problem, schizophrenia may be triggered by many rare mutations that cause subtly different variants of the disease. "What is beginning to emerge is that a lot of the risk of brain diseases is conferred by rare [genetic] deletions," [study author Kari] Stefansson said.... The new focus on rare mutations suggests that natural selection is highly efficient at removing schizophrenia-causing genes from the population. Despite selection against the disease, according to this new idea, schizophrenia continues to appear because it is driven by a spate of new mutations that occur all the time in the population.
The two studies, both published in the journalNature [subscription required], are a small step forward in the struggle to understand schizophrenia. The disease has posed a mystery to researchers, as it
clearly involves a strong genetic element, often running in families. And its prevalence in the population tends to remain steady over time, at about 1 percent. Yet people with schizophrenia usually start having symptoms -- hallucinations, thinking problems and more -- in young adulthood, so many do not end up having children. So how does it remain so common in successive generations? [Boston Globe]
These new findings suggest that in at least some cases, the disease may be caused by these rare mutations that occur spontaneously during early development. But researchers caution that other cases of schizophrenia may be caused by common mutations that are inherited, and which interact with environmental influences.
There are likely to be many more genetic variants that are associated with schizophrenia coming to light – maybe as many as thousands, says [one study author David] St Clair. "I wouldn't have said that even a year ago, but that's the way it's looking." That means that a simple genetic test is still a long way off. But [researchers] believe that identifying some of the genes in the pathway – and where they can be found – is already a big step forward [New Scientist].
For more on schizophrenia and a radical approach to its treatment in teenagers, check out the new DISCOVER article, "Can Schizophrenia Be Cured Before It Starts?" Image: National Human Genome Research Institute
