Statement from researchers and consumers from the Collaborative on Fatigue and related symptoms Following Infection (COFFI)
The DecodeME study is the largest of its kind to date, but its findings need careful interpretation. They are not a groundbreaking, and we are concerned with the way these preliminary findings are being promoted. Once replicated, they may be another piece of the puzzle in understanding mechanisms behind ME/CFS.
Background
We know the condition is real and our genes are implicated
1. We recognise the need for high quality research to better understand the underlying biological mechanisms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
2. A recent genetics analysis in people with ME/CFS was made publicly available as a pre-print prior to peer review. This research is a helpful contribution to the knowledge base. The researchers sought genetic markers associated with the condition through a genome-wide association study (GWAS). This study, called the DecodeME project, has attracted press headlines and many contain strong statements from the study authors, for example:
“These results are groundbreaking. We have gone from knowing next to nothing about the causes of ME/CFS to giving researchers clear targets.” (Sonya Chowdhury, author).
"For so long people with ME/CFS have been told it's all in their head. It's not. We see it in their blood." (Chris Ponting, senior author).
3. The messaging has created widespread excitement and raised expectations in both the research and patient communities. The research has been presented as ground-breaking and heralding an imminent cure.
COFFI response
4. The researchers of the Collaborative on Fatigue and related symptoms following Infection (COFFI – www.coffi-collaborative.com) and their Consumer Advisory Group (CAG) were surprised by the hyperbole in reporting the findings. COFFI researchers and consumers have recognised this condition as real for more than 25 years and recognise that the research into the genetic link has long been established, although perhaps not with specific predisposing genes implicated.
5. In the light of these concerns, the COFFI consumer advisory group and the COFFI researchers provide a commentary.
COFFI consumers’ commentary
Views on the hyperbole
6. The effort put in and the size of the study is impressive and this adds useful knowledge. However, the study authors state that showing an association with genes somehow demonstrates that the condition is “real”. This is not particularly useful, because we already recognise the condition is real.
7. Genes are part of the picture, but there is a danger with this emphasis. The statement “we see it in the blood” implies for consumers that genes “cause” the condition. This statement may contribute to some patients believing nothing can be done unless we get a biomedical cure.
8. This narrative may lead them to believe the condition cannot be influenced by approaches based on a biopsychosocial approach, which is clearly helping many people to reduce symptoms and some to recover.
9. The hyperbole around research showing genes influence risk in ME/CFS has happened before: 20 years ago a press release stated that researchers were close to finding the genes responsible for ME/CFS, and that they expected to have treatments within a year. At that time, patients waited for a cure, but nothing appeared, and patients deteriorated in the meantime making recovery harder.
Research on practical measures that help needed
10. The article states there are no effective treatments, but this is incorrect. There are a range of strategies for rehabilitation, drawing on the biopsychosocial explanation of this condition. These include cognitive behaviour therapy, approaches to safely increase activity and mind-body approaches. The research indicates these options may help people reduce symptoms and ensure some recover. Putting patients on hold with this condition awaiting a drug could be unhelpful.
11. We also know that recovery is possible, and question why recovered patients were not included in the genetic analysis. Maybe this is a question to be added in further research. It would be interesting to know whether genetic, environmental, or psychological factors influencing the occurrence, severity and chance of recovery.
12. In summary, the Collaborative consumers noted the emphasis on genetics does not help people currently with the condition. Genetic studies can expand understanding, but people with ME/CFS also need practical answers now. Research into treatments, rehabilitation, and support strategies must remain a priority.
COFFI researchers’ commentary
Findings interesting but not ground-breaking
13. The COFFI researchers considered the study. We note its size, and that the genetic traits related to brain and immune function, which supports what we already know.
14. We all recognize that persistent fatigue, like many conditions (including cardiovascular disease and depression) has a genetic component, so genes can influence risk of developing the condition. We also know that this genetic contribution to risk is likely not to be from one gene but from several (“polygenic”).
15. We note that the eight genetic markers reported in the pre-print were associated with the condition, but the size of the effect found were modest. This means that the same genetic markers were also present in many healthy control participants. This makes their isolated interpretation limited. Further analysis looking at various gene combinations may be more informative.
16. Like other conditions such as heart conditions or depression, the heritable component, the genes, are only one influence on the risk of developing the condition. Most human illnesses result from very complex interplay between many genetic factors, and things that people are exposed to throughout their life.
17. We also know that genetic influences can be altered by environmental exposure. This phenomenon, known as epigenetics (how our environment can switch genes on or off), was not examined.
Patients varied, and the study requires peer review and replication
18. We note that the ME/CFS diagnosis was based on self-report. This means the patients will be quite varied, and only a small minority reported onset with a documented infection, whereas fatigue conditions can arise because of many different precipitating causes. This wide variation in the patients may well lead to flawed positive associations with genes that have no influence; and on the other hand, may miss actual associations.
19. The findings are yet to be peer reviewed, which may alter the interpretation, and all good science the analysis needs independent replication. The DecodeME researchers themselves state they were unable to identify the specific genetic markers in other large data samples they had access to and this is important.
20. In summary, this large study has some interesting findings with specific genes identified. This is a contribution to what we know already, and needs replication.
