Over 100 genetic loci for schizophrenia found

August 5, 2014 - 06:06

The largest current study of schizophrenia has located a number of genes that contribute to raising the risk of the serious mental disorder.

The genes of over 150,000 persons round the world have been analysed to find specific sequences which contribute to the inheritable disease schizophrenia. (Illustration: Microstock)

Genetics play a key role in the development of schizophrenia.

But the serious disorder does not spring from a single 'schizophrenia gene'. 

Nevertheless, scientists have now found a large number of locations or sequences on the human chromosome ― genetic loci ― which all contribute to a higher risk. If a sufficient quantity of these loci is present in a person’s chromosomes, he or she is disposed toward developing schizophrenia.

They were born that way.

This was clarified after the completion of the largest international research project ever carried out on a serious mental disorder.

“Working together, researchers from many parts of the world have made a breakthrough in research on schizophrenia,” says Professor Ole A. Andreassen. He is a researcher at NORMENT – KG Jebsen Psychosis Research Centre at the University of Oslo and the Oslo University Hospital.

150,000 persons examined

The genes of about 150,000 persons round the world were studied to expand knowledge about genetic causes of schizophrenia. About 1,000 of the test persons are Norwegian.

“No research project of such dimensions could have been possible without international cooperation among many countries,” says Andreassen.

Researchers from four hospitals and institutes in Oslo as well as from hospitals in Stavanger and Kristiansand took part in the monumental study.

Schizophrenia has been a mystery

Schizophrenia has long been known to have a genetic component, as it tends to run in families, but the exact details have been shrouded in mystery. 

Scientists have now shed considerable light on the problem by finding 108 conservatively defined loci that with a high degree of certainty are important to the development of schizophrenia. 

A total of 83 of these have not previously been linked to the disease.

“We now have solid data and robust research findings,” says Andreassen enthusiastically.

“This is a study that can be repeated by other researchers and they will obtain the same results. That isn’t always the case in research on psychiatric genetics,” adds Andreassen, who led the Norwegian participation in the international project.

Many small gene variations behind the disease

A large number of genes are in play when a person develops schizophrenia.

This is the most salient finding, according to Andreassen.

“Each of these 108 genes has little individual effect. Changes in a whole number of them together are needed to raise the risk of a person developing the mental disease. If a person surpasses a certain threshold for genetic disposition, and stressful factors in their social environment are present, they can get the disease.”

“If this inherited vulnerability is way over the threshold, the risk of mental illness rises even more. A person can then become ill almost without experiencing anything in their lives that sets it off.” 

The research project found that a person with many of the pertinent schizophrenia gene variations which have now been identified runs ten to 20 times the risk of developing schizophrenia, compared to persons without these genetic codes.

Possible to make biological findings in schizophrenia

This research cannot be used yet to carry out a genetic analysis of a person, and thus say anything useful about the risk of developing schizophrenia.

The major breakthrough extends understanding of biological factors which have roles in the process of the disease.

By identifying so many gene variations the researchers now have the opportunity to map which disease mechanisms are present. An example of a result that could open opportunities for future treatment is when the scientists now see a connection between the dopamine receptor DRD2 and schizophrenia. 

Another important discovery from the project was the finding that schizophrenia genes are active with regard to our immune system.

As for possible new drugs against the disease, Andreassen says:

“We now have several effective medications for schizophrenics. But no great improvements on these drugs have been made since the 1960s, and many of them entail serious side-effects. There’s obviously a need for improvements here and we firmly believe this research will open new doors.”

Looking through 10 million gene variations

Over 300 authors are behind the article, which was published in Nature. Several Norwegians were among them.

About 500 schizophrenics and 500 healthy people in Norway participated in the study, with genes in biobanks. 

The scientists searched through about 10 million gene variations among the 150,000 individuals in the project. This encompassed all the most common gene variations in a population.

One percent schizophrenia

The symptoms of schizophrenia usually pop up initially when people are young adults.

An estimated one percent of the population develops schizophrenia.

Patients with the disease can suffer delusions, for instance experiencing that the TV is speaking directly to them, or that persons or cars outside their homes are keeping them under surveillance.

Schizophrenics can also hear voices or see things no one else sees – suffer hallucinations.

Other symptoms of schizophrenia are dulled emotions, lack of will, the inability to enjoy anything, lack of attention, disassociated speech and pointless or repetitive behaviour.

In simple terms, schizophrenia impairs thoughts and cognition, whereas bipolarity or manic depression for instance impacts emotions.

Many schizophrenics suffer bouts of depression and anxiety.

This is a debilitating disorder which makes it hard to hold jobs so poverty is a common result. About 40 percent of schizophrenics also abuse drugs and alcohol.

Schizophrenia can entail numerous combinations of symptoms. Some medical researchers contend that it is not a single disorder or syndrome, but rather a combination of many.

On average, the expected life span of a schizophrenic is reduced by 10 years.

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Read the Norwegian version of this article at forskning.no

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Translated by
Glenn Ostling

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