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Study offers insight into genetics of schizophrenia

10:30am Tuesday 22nd July 2014 content supplied byNHS Choices

"More than 100 schizophrenia genes have been pinpointed," reports the Daily Mail. In one of the largest studies of its kind, researchers have gained further insights into the genetics of the condition, which it is hoped could lead to new treatments.

Researchers have identified genetic differences at 108 positions in the genome (the complete set of DNA that "defines" an individual organism) that are more likely to be present in people with schizophrenia.

The study compared the genetic make-up of more than 36,000 people with schizophrenia with that of more than 110,000 controls. They found differences in 108 positions in the genome, 83 of which had not previously been reported.

A particularly interesting finding was evidence of genetic differences in genes active in the immune system. Whether or not the immune system plays a role in the development of schizophrenia is a possibility not previously considered by most experts.

This study provides further evidence of a genetic element to the condition, but it does not prove that the genetic differences actually cause schizophrenia.

However, it is hoped these results will lead to new avenues of research that can be explored, and may eventually lead to better treatments for the condition.

 

The genetics of schizophrenia

It has long been suspected the cause of schizophrenia, which affects 1% of the population, is a combination of multiple genetic and environmental factors.

 

Family studies have shown the increased risk from having one parent with the disorder is about 7%, but this increases to 46% if both parents are affected. Other studies have shown that if one identical twin develops schizophrenia, the other has a 48% risk, even if they are raised separately.

Where did the story come from?

The study was led by researchers from Cardiff University and involved hundreds of researchers from around the world as part of the Schizophrenia Working Group of the Psychiatric Genomics Consortium.

It was funded by the US National Institute of Mental Health and grants from governmental bodies and charities.

The study was published in the peer-reviewed journal Nature.

The UK media reported the study accurately. The Independent's coverage was particularly informative, providing independent expert opinions on the findings.

It also included a balanced viewpoint from charities highlighting the need for holistic care regardless of whether new drug treatments are developed.

People living with schizophrenia usually require a combination of medication and talking treatments, such as cognitive behavioural therapy (CBT), to better control their symptoms.

 

What kind of research was this?

This was a genome-wide association study that aimed to combine all of the data from published and unpublished studies that had analysed the genetic make-up of people with schizophrenia, comparing this data with the genetics of people who do not have the condition.

This type of study is able to identify small variations in genes present more frequently in people with a particular disease, compared with people without the disease.

But it is only able to show an association and cannot prove that the genetic variations found cause the disease.

This type of study is useful, however, as it can point to new areas that may be involved in the disease process. These can then be investigated further in other types of studies and could eventually lead to new treatments.

 

What did the research involve?

The researchers obtained data from all the available genome-wide association studies of people with schizophrenia from around the world. This included 46 European case-control samples, three east Asian case-control samples, three European family-based studies, and results from Icelandic population studies.

Overall, the genetic make-up of 36,989 people with schizophrenia was compared with that of 113,075 healthy controls. This involved sophisticated analysis looking at 9.5 million genetic variants.

 

What were the basic results?

The researchers found variations in 108 loci (positions in the genome) that met genome-wide significance, 83 of which had not been previously implicated in schizophrenia. Genome-wide significance means there is a statistically significant possibility a variation is associated with a condition.

Of these 108 loci, 75% coded for proteins. Several of the proteins are thought to have a role in schizophrenia. Variations were found in a gene that codes for the dopamine receptor, the main target of medication to treat schizophrenia, and other genes involved in neurotransmission and synaptic plasticity.

The researchers also found variations occurred in genes expressed in the brain, as well as in genes expressed in the immune system.

 

How did the researchers interpret the results?

The researchers concluded that they have identified variations in genes expressed in the brain. More specifically, they found variations in the gene that encodes a protein that has been a target for drug therapies for schizophrenia for years, as well as in other genes involved in neurotransmission.

They have also found variations in genes expressed in the immune system, which they say provides "support for the speculated link between the immune system and schizophrenia".

However, they are also excited about the fact there are variations in a number of other genes and how this creates "the potential to provide entirely new insights into aetiology [the cause of the disease]".

 

Conclusion

This large genome-wide association study has found genetic variations in 108 loci more likely to be found in people with schizophrenia than in healthy controls.

While some of these variations fell in genes that code for proteins that are already targets for drug treatments for schizophrenia, variations at 83 of the loci had not previously been implicated as being involved in schizophrenia. This provides new insights for further research.

The study's strengths include the large number of cases and controls involved.

But this study cannot prove that these genetic variants cause schizophrenia. It remains likely that a combination of environmental factors and genetic susceptibility increases the risk of the condition.

A further consideration is the huge variability in the level of severity and the type of symptoms that can be present within the "umbrella" diagnosis of schizophrenia.

It is hoped the identification of these genes will pave the way towards a greater understanding of this complex condition.

Read more about schizophrenia, the current treatments for the condition and the available support.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Summary

"More than 100 schizophrenia genes have been pinpointed," reports the Daily Mail. In one of the largest studies of its kind, researchers have gained further insights into the genetics of the condition, which it is hoped could lead to new treatments.

Links to Headlines

New DNA hope on schizophrenia: Discovery of 100 genes could help to transform treatment for the condition. Daily Mail, July 22 2014

DNA hope on schizophrenia: Research breakthrough points at over 100 genes. The Independent, July 22 2014

'Eighty new genes linked to schizophrenia'. BBC News, July 22 2014

Schizophrenia gene study: what we've learned is how little we know. The Daily Telegraph, July 22 2014

Links to Science

Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. Published online July 22 2014

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