The genetics of schizophrenia
by Thomas Kabir
To say that schizophrenia is a controversial diagnosis would be putting it mildly. Almost everything relating to schizophrenia has been contested, often ferociously. Putting that to one side, there is a lot of research into schizophrenia particularly to understand causation and treatments. We have known for a while that there is some evidence that schizophrenia runs in families. We have just got a bit closer to perhaps finding out why.
In July 2014 the results of some research led by researchers at the University of Cardiff was published in the journal Nature. The research is part of a larger programme of work being carried out by the Psychiatric Genome Consortium.
The research was reported on in most of the daily newspapers such as the Independent (‘DNA hope on schizophrenia: Research breakthrough points at over 100 genes’). The paper got quite a bit of attention in the news too with the BBC reporting on it as well as other broadcasters over the world.
So what was so exciting? Well the paper looked at the DNA of 37,000 people with schizophrenia in 35 different countries. These people’s DNA was then compared to 110,000 people who did not have schizophrenia. The researchers found around 108 ‘points’ across around 80 genes where there were significant differences.
In the world of psychiatric genetics this is a breakthrough -check out this chart. The 2014 study means that we now know of five times the number of genetic differences between people who do and do not have schizophrenia compared with 2013. To find out more about what exactly a gene is please click here. If you would like to find out more about the actual study then please, please, (I beg you!) read this great summary of the paper on the NHS Choices website.
Aside from this it is important to note that all human beings pretty much have the same set of around 24,000 genes. There are some differences between men and women but these not large. So if we all pretty much have the same genes how come we all look so different? Good question. It’s complicated. It’s partly genetics and partly the environment. Genes come in lots of varieties. It’s a bit like hair colours. Within any one colour there are thousands of different shades. And so it is with genes. There are many different versions of the same gene. This is why one person may be blonde but another brunette.
The environment obviously plays a big part too. If you grow up in the vicinity of a nuclear disaster zone without much food then you are likely to turn out a bit differently to someone raised in a very unpolluted and affluent area.
When scientists speak of finding a ‘new’ gene for something (say schizophrenia) they do not usually mean that they have discovered an entirely new gene. Usually they mean that they have discovered a particular version of a gene that has identified as having a role to play in something. In this context the bottom line is that the researchers from the consortium led by Cardiff University have found around eighty particular versions of genes that are more commonly found in people with schizophrenia. There is no such thing as a “gene for X, Y, or Z” as we all pretty much have the same set of genes. What is actually often meant is that “if you have this particular version of a gene then it may increase your likelihood of having X, Y or Z”.
But why is this research important? Well nobody is claiming that this research is going to lead to a better way of helping people with schizophrenia anytime soon. But finding differences between someone with a health condition and those that don’t is very often the first step towards developing new ways of managing and treating people.
Take breast cancer as an example. Two genes have been discovered called BRACA1 and BRACA2. If you have these genes you are at a higher risk of developing breast cancer compared with the general population. Once these genes were discovered, a way of testing if people had them was quickly found. Testing people for these two genes together with other advances has meant that survival rates for people with breast cancer have improved significantly.
There are significant ethical issues that arise from genetic research. Could people who test positive for genes that might cause disease be discriminated against? Could people refuse to employ you based on your genes? What do you do if you want to have a family? There are so many ethical issues that arise from the genetics of mental health conditions. If you would like to know more please do read this 1998 report from the Nuffield Foundation.
There are other problems too. Genetics is massively complicated. Even if you do test positive for a disease linked gene, all it does is increase the chance that you might get the illness. In fact there is only one condition (Huntingdon’s disease) where if you test positive for the gene you will get the disease. It’s a numbers game. Genetic testing only tells you something about your ‘risk’ of developing an illness or disease. Aside from this it’s clear that genetics is not the whole answer. What happens to you in your life also has a big effect. Needless to say this is particularly the case in mental health.
The genetics of mental health is not well understood. In fact we are probably behind many other areas of health here. This could be for two reasons. 1. Mental health problems don’t have a strong genetic component. 2. Not enough research has been done into the genetics of mental health. Things are changing though and the Nature paper should be welcomed.
What is a bit worrying is the lack of lived experience in genetic research. From what I have seen, service user and carer involvement in mental health genetics is relatively underdeveloped. I wouldn’t say that there is no involvement in research into the genetics of mental health, I just don’t see very much. And given the complexity of genetics research and the issues that it raises, we probably need quite a bit more service user and carer involvement not less.
A number of articles were published about the research in the July 24th 2014 edition of Nature to accompany the research paper itself. Whilst one of the articles did include a very brief account of someone who had schizophrenia there was little direct focus on who’s surely most important here: people with schizophrenia. To their credit, the following week Nature published an article entitled ‘cause is not everything in mental health’, by someone with lived experience of mental illness in response to the research published in the July 24th edition.
On the other hand there is no lack of goodwill or of people trying to explain what genetic research means. In fact there are some wonderful and innovative resources available (for example: http://www.geneticseducation.nhs.uk/)
But history teaches us that we that we need to be very careful. For example, there have been suggestions in the past that people with ‘undesirable or defective’ traits should be sterilised to prevent them from passing these on to future generations. A whole field of study developed around this called eugenics. And we aren’t simply talking about the Nazi’s here. Winston Churchill was in favour of “the confinement, segregation, and sterilization of a class of persons contemporarily described as the “feeble minded.” . If you don’t believe me click here
There is massive scope for the findings of genetics research to be badly communicated. Both geneticists and the press have probably been guilty of this in the past. The results of the ensuing misunderstandings can be severe. There are certainly people who have made bad choices or decided not to have children based on newspaper headlines or a false interpretation of genetic tests. Many of these issues have been tackled admirably in areas of health, such as cancer, but not so much in mental health. We would do well to actively involve people with lived experience of mental illness very early on in genetic research studies to proactively work through all of the issues that I have raised in this article, and more. Indeed a report from INVOLVE shows that “public involvement throughout a study can help to make research more ethical”.
Doing this would ensure that we have some worked out solutions and approaches to the particular issues that genetics research into mental health raises. Who could be better placed to help develop these solutions and approaches than people with actual lived experience of mental illness?
Many abuses in medical research have happened when things are ‘done to’ rather than ‘done with’ people. I would never ever want to imply or suggest that the researchers from the Psychiatric Genome Consortium have done anything wrong -far from it, but we need more involvement of people with lived experience of mental illness involved in genetic research and we need it soon.
I don’t want to end on a downbeat note. We need to understand mental illness better. The paper published in Nature potentially brings us one step closer to understanding what part genetics plays in schizophrenia. To all the researchers of the Psychiatric Genome Consortium I say ‘thank you’!
Dr Thomas Kabir – Public Involvement in Research manager.
To listen to a great Naked Genetics podcast on recent advances in psychiatric genetics please click here.
OMIM (www.omim.org). OMIM is a database of all genes known to play a part in any illness or disease. To have a look at a full lust of genes sorted by illness or disease click here.
‘Mental health: Depression needs large human-genetics’ studies by Steven Hyman. Nature, November 2014. Volume 515 p189-191. Please click here to read the full article.