Blog: Could genes be the key to finding what causes ME/CFS?
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What role do genes play in the development of ME/CFS? And what genes, proteins and bodily processes should we be looking at? Geneticist Cindy Boer of Erasmus Medical Centre hopes to answer these questions in her ME/CFS study, which aims to identify the genetic basis for the disease. She believes this will greatly enhance the prospects for treatment.
TheME/CFS research programme funds biomedical research on the causes, diagnosis and treatment of ME/CFS. The first studies got underway in 2023. In this series of blogs, the researchers tell us more about what they are doing, and what their ME/CFS study aims to deliver. A new blog will be published each month; this is the third in the series..
For a better understanding of ME/CFS, we have to look beyond visible symptoms. Things that happen out of sight, in the body, give us more insight into biological processes and how ME/CFS comes.
We still know too little about ME/CFS in terms of genes and proteins. If we knew which genes and proteins were involved in the disease, this might eventually give us prospects for treatment. Over the next few years, geneticist Cindy Boer will be looking into the genetic aspects underlying ME/CFS in the ZonMw-funded project.
Genes and environment
‘Lots of researchers think that ME/CFS happens because of an external trigger, like a viral infection. But that’s not always the case. Some people become ill without the occurrence of a viral infection. This indicates there are more factors at play if it comes to whether a person develops the disease. Some studies, like cohort studies of twins or families, show that DNA probably plays a role in ME/CFS. In other words, someone can have certain genetic variations in their DNA that increase their chances of developing ME/CFS in response to an external trigger. As soon as that person contracts a viral infection, they may be at higher risk of the disease than someone who does not have these variations, or has fewer variations. It is estimated that DNA accounts for 30 to 50% of an individual’s risk of getting ME/CFS. I expect that we are able to discover which genetic variations are involved in ME/CFS during the four years of this project.'
From gene to protein
The nucleus of every cell in the body contains information in our DNA, which tells each cell what to do. For the cell to work properly, the DNA has to be read and translated into proteins, the building blocks of our bodies. DNA can be divided into genes, each of which contains the code for one protein. Genes are therefore the blueprint for the production of proteins, which are involved in almost every process in the body: the repair, growth and maintenance of cells, hormone production, the immune system, transport by red blood cells, muscle building. They are also the precursors of neurotransmitters in the brain.
The human genome contains around 20,000 genes, and every person has a unique set of genes in their DNA. Changes, or variations, in DNA can affect proteins, making them less effective, or entirely ineffective. This, in turn, can cause illness.
‘We will be conducting a genome-wide association study (GWAS) to find out which genetic variations play a role in ME/CFS. We’ll be looking at which variations occur more frequently, or exclusively, in people with ME/CFS, compared to people without ME/CFS. We need a huge DNA dataset to do this properly and reliably, with data from hundreds to thousands of people with ME/CFS and hundreds of thousands of people without the disease. Existing datasets, like that from theLifelines cohort study, don’t include enough people, so our first goal is to collect DNA information from as many people as possible. We plan to do so by collaborating with a range of existing cohort studies all over the world. We’ve already made a start, and have reached out to other researchers setting up major projects in Europe and America. They have indicated their willingness to make their datasets available to our study.'
Role of DNA in ME/CFS
‘We won’t be able to say anything about the role of genetic variations and genes in ME/CFS until after we have analysed a huge quantity of data. The questions I’ll be looking at are: What genes and biological processes are involved in ME/CFS? And is there any overlap with related conditions? We’ve developed specific methods for establishing whether there are genetic similarities between ME/CFS and post-COVID or Q fever fatigue syndrome patients, for example. If we do identify any similarities, this means that the same biological processes might be occurring in these diseases.'
First DNA variations
‘We expect to have the first results on the genetic variations in early 2025, then we’ll have an initial idea of any differences in DNA between people with ME/CFS and people who don’t have the disease, but perhaps have another medical condition. Then we can look for the genes involved, to find out which biological processes play a role in ME/CFS. Could it be something other than the immune system or metabolic system? Could it be something happening in the brain? We’ll also be looking at proteins and biological activity in cells, in the hope of discovering differences between people with ME/CFS and other people.'
Hope of treatment
'In the fourth year of the project we’ll be looking at the possibility of treatment, based on what we’ve found. If the genes we’ve identified and the bodily processes involved also play a role in another disease, it could be that drug treatment is already available. Or we might have identified a clear gene or process that is linked to ME/CFS. That gives us the best chance of developing effective medication, but that will be in the future. And if we discover that there are no similarities with other illnesses, that will be helpful too, though the road to a drug treatment will be longer then, of course.'
Afbeelding
Patients have more understanding of the symptoms and effects, so they can provide information on this.
‘Patient representatives have been involved from the start, in the research proposal and the questionnaires. We will keep them informed of our search for genetic variations and genes. And they will help us interpret the results. Patients have more understanding of the symptoms and effects, so they can provide information on this at the meetings they attend. They will also help us communicate news of our study to patient organisations.'
Part of the ME/CFS Lines consortium
This project is one of the studies in the ME/CFS Lines consortium. For more information on the consortium, and other studies, visit theproject page of the ME/CFS Lines consortium. We will also be publishing our results onthe ME/CFS Lines consortium website.
About the researcher
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Cindy Boer
Cindy Boer is a biologist and geneticist who works as a scientific researcher at Erasmus MC in Rotterdam. She specialises in genetic research among different populations, focusing on identifying whether genes play a role in people’s risk of developing certain diseases. Her PhD research investigated whether and, if so, which genetic variations play a role in osteoarthritis. She discovered a variation in DNA that increases a person’s likelihood of developing osteoarthritis, which is linked to vitamin K. She is particularly motivated to perform genetic research on ME/CFS, as she believes that genetics could reveal more about the biological cause of the disease. She believes great benefits are to be gained from obtaining information from the genome in order to better understand this disease, which still receives insufficient attention.
For more information about the research project and the ZonMw research program ME/CFS, please refer to the pages below.
- Go to the project page
- Go to the consortium website
- Go to the ME/CFS Research Programme page
- Go to the fatigue theme page
Text: Ilse Bos, Photography: Robert Tjalondo, private archive Cindy Boer
