Rare and damaging genetic mutations increase the risk of developing schizophrenia, scientists have said. They are also associated with lower levels of education.
Schizophrenia is a highly heritable psychiatric illness. About 1 in 100 people get diagnosed with the disease but for people who have a parent affected, this figure increases to about 1 in 10. However, the fertility rate of schizophrenia sufferers is lower than average, meaning the genetic mutations linked to the disease that they could potentially pass on to offspring are rare.
The problem is that, because they are rare, it is more difficult to assess the contribution of these mutations to the disease.
In a paper published in the journal Nature, scientists have studied the genome of a large cohort of people, including schizophrenia patients, to pinpoint if rare specific genetic mutations could increase the risk of developing the mental health disorder.
Additionally, another study published in the same journal has examined whether these mutations were tied in any ways, and how, to the number of years spent in education.
In large group of 12,332 Swedish individuals, researchers led by Steven McCarroll and Giulio Genovese from the Broad Institute of MIT and Harvard, examined the protein coding sequences of DNA. Some of the people in the cohort had been diagnosed with schizophrenia.
Investigating the impact of rare damaging mutations, they focused on rare mutations observed in their cohort but never in the DNA sequences of a comparative group of individuals without psychiatric disorders.
They discovered that the rare mutations were more common in patients with schizophrenia overall. The mutated genes identified affected proteins that were expressed specifically in the synapses of brain cells but not in other organs. This suggests that having a rare mutation is tied to a greater risk of suffering from schizophrenia – it is likely that it plays a role in the development of the disease.
Years in education
A controversial topic to study is whether our genetics can change the number of years we spend in educations. Because environmental factors come into play, and success in education can depend on cognition but also on personality, it is often difficult to untangle what role rare mutations – if any – plays on educational attainment.
Scientists led by Andrea Ganna, from Massachusetts General Hospital, investigated the link between rare damaging mutations and years of educational attainment among 14,133 healthy individuals from the general population in Sweden, Estonia and Finland. The focused on genes which are very sensitive to changes in their DNA - in other words which can have a very different expression with just a slight DNA change. These mutations were very rare among the thousands of individuals studied.
They found that each damaging mutation they studied in one of these genes was associated with three fewer months of education. This effect was stronger among genes which are highly expressed in the brain. People who had rare and damaging mutations associated with these genes were more likely to have six fewer months of education.
As with schizophrenia, it is not possible to blame lower education levels only on rare genetic mutations. Cognition, personality and psychology – factors which are all implicated in educational attainment – may be affected by these mutations although it is not yet clear to what extent. Environmental factors also plays a role to develop the disease and influence how much education we are able to get.
To get a better idea of the role of these different processes, even larger studies are needed to pinpoint specific genes and specific brain processes. Researchers will have to investigate in greater depths the overlap between rare genetic risk for psychiatric disease and typical variation in cognitive function.