Is schizophrenia risk 'around 80% genetic'?

"Genetics account for almost 80 per cent of a person's risk of developing schizophrenia, according to new research," the Mail Online reports. That is the main finding of a study looking at how often schizophrenia affected both twins of a pair, looking at identical and non-identical twins.

Schizophrenia is a serious mental health condition that can cause delusions and hallucinations. There is no single "cause" of schizophrenia. It is thought to result from a complex combination of both genetic and environmental factors.

The researchers looked at twins born in Denmark and found that if one identical twin had schizophrenia, the other twin (with the same genes) was also affected in about a third of cases. For non-identical twins, who only share on average half of their genes, this was true only in about 7% of cases. Based on these figures, the researchers calculated that 79% of the risk of developing schizophrenia was down to their genes.

While the findings suggest genes do play an important role in schizophrenia, this is only an estimate and the true picture is likely to be more complicated. Environmental factors clearly still have an influence on whether the person actually develops schizophrenia.

If you do have a history of schizophrenia in your family, this doesn't mean you will automatically get the condition yourself. But it may be a good idea to avoid things that have been linked to the condition, such as drug use (particularly cannabis, cocaine, LSD or amphetamines).

Where did the story come from?

The study was carried out by researchers from the Center for Neuropsychiatric Schizophrenia Research at Copenhagen University Hospital in Denmark. Funding was provided by the Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, and Lundbeck Foundation Initiative for Integrative Psychiatric Research.

The study was published in the peer-reviewed journal Biological Psychiatry, and is available to read for free online.

The Mail's report that: "The findings suggest the genes we inherit play a far bigger role than previously believed and mean the seeds are sown before birth" isn't strictly correct. The estimates from the current study are similar to those from some previous studies.

What kind of research was this?

This was a twin cohort study using data from the Danish Twin Register combined with the psychiatric registry, aiming to better quantify the extent to which schizophrenia risk may be explained by the genes we inherit. Previous studies have suggested that genes play an important role, but researchers wanted to use some updated statistical methods and newer data to come up with a more up-to-date estimate.

Both genetics and environmental factors are thought to play a role in the risk of schizophrenia. Twin studies are a standard way to estimate the extent to which genetics plays a role. Both identical and non-identical twins may be assumed to have the same environmental exposure. However, identical twins have 100% of their genes in common, while non-identical twins share only 50% on average.

Therefore if identical twins are more alike than non-identical twins, marked differences in health outcomes are likely to be down to genetics. Researchers used statistical methods to estimate what role genes play in the development of a particular characteristic (called "heritability").

Previous studies show that schizophrenia affects both members of identical twins in 41% to 61% of cases, but only 0 to 28% in non-identical twins. A previous pooling of twin studies has suggested that the "heritability" of schizophrenia is 81%.

It is worth bearing in mind that this type of twin cohort study makes various assumptions to simplify the picture.

It assumes that genes and the environment do not interact. This assumption may result in over-estimating the impact of genes. For example, it could be the case that people with a specific genetic profile are more likely to use drugs. Drug use (an environmental risk factor), rather than the genes directly, could then increase the risk of schizophrenia.

Also, the results obtained are very dependent on the environment the twins are living in. So results would likely differ if the same study were carried out in different societies at different time points throughout history.

Finally, this type of study does not identify specific genes that may be involved in the risk of schizophrenia.

What did the research involve?

The Danish Twin Register, started in 1954, includes all twins born in Denmark. The Danish Psychiatric Central Research Register includes data on all psychiatric hospital admissions since 1969, and all outpatient visits since 1995. Diagnoses in the register are based on the long-established International Classification of Diseases (ICD), which is a way of classifying diseases according to standard criteria.

The researchers used data on 31,524 twin pairs born up to the year 2000, linked with the psychiatric registry data, and knew whether they were identical or not.

They identified the twins who had been diagnosed with schizophrenia or schizophrenia spectrum disorders (this means not fulfilling diagnostic criteria for schizophrenia, but having a disorder with similar characteristics).

They then looked at how many of these diagnoses affected both twins in a pair. They used statistical methods to estimate how much of a role genes played in the development of schizophrenia. One of the new features of the methods used was that they took into account how long each twin had been followed up.

The researchers' results only apply to schizophrenia diagnosed up to the age of 40.

What were the basic results?

448 of the included twin pairs (about 1% of the sample) were affected by schizophrenia, and 788 were affected by schizophrenia spectrum disorders. Average age of diagnosis of these conditions was about 28 or 29 years.

The researchers found that if one identical twin was affected by schizophrenia or schizophrenia spectrum disorders, the chance of the second being affected was about a third. For non-identical twins, the chance was far lower – only 7% for schizophrenia and 9% for schizophrenia spectrum disorders.

The researchers estimated that in the population studied, about 78% of the "liability" for schizophrenia and 73% for schizophrenia spectrum disorders could come down to genetic factors. This means that a high proportion of the co-twins may be carrying genes that make them "vulnerable" to the condition, even if they haven't developed it in this study.

How did the researchers interpret the results?

The researchers conclude: "The estimated 79% heritability of schizophrenia is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader [range of] schizophrenia spectrum disorders. The low [co-diagnosis] rate of 33% in [identical] twins demonstrates that illness vulnerability is not solely indicated by genetic factors."

Conclusion

This study explores how much of the risk of developing schizophrenia or related disorders may be explained by genetics.

It shows that schizophrenia and related disorders are quite rare – affecting about 1% of the general population.

Their observed co-diagnosis rate in both twins – about a third for identical and less than 10% for non-identical twins – was lower than has been observed in other studies. This seems to suggest that while a high proportion of an individual's susceptibility may come down to hereditary factors, environmental factors must still be play a substantial role.

This type of study makes a number of assumptions to simplify the picture, and these may not accurately portray reality. For example, it assumes that identical and non-identical twins would share similar environmental exposures. However, this may not be the case. It also assumes that genes and the environment do not interact, but in reality, people with different genetic makeups may react to the same exposure in different ways.

Other reasons for the low co-diagnosis rate could be, as the researchers acknowledge, down to study methods. For example, some may have had different severity or presentation of illness influencing diagnosis. The study also does not have lifelong data for all of the twins. Though most people with schizophrenia are diagnosed before 40 years of age, longer follow-up times would be ideal.

One final point: estimates that come out of this type of study are dependent on the environment the twins are living in. So results would likely differ if the same study were carried out in very different societies, or at different time points throughout history. Though this study benefits from using a large population-wide registry, study members were all Danish residents. The findings may not apply to different populations, with different ethnic and cultural makeups.

The study will add to the large body of literature exploring the role of hereditary and environmental risk factors for schizophrenia. However, it certainly doesn't mean we fully understand the causes of the condition, including the impact of environment on this condition.