Background
ME/CFS is thought to affect approximately 250,000 people in the UK, with 25% of these people house- or bed-bound. People with ME/CFS experience higher levels of impairment in the ability to complete daily tasks, and lower levels of wellbeing, compared with conditions including depression, cancer and rheumatoid arthritis (RA). ME/CFS is also associated with a high economic cost to the individuals with the disease themselves, but also their families and the wider economy. Despite this, the causes of ME/CFS remain unknown, as do effective treatments for the illness.
While previous studies have identified biological differences between people with ME/CFS and those without, these studies have often been small in size and require replication in different populations of people with ME/CFS for the results to be verified. In addition, the differences identified may be a result of the ME/CFS disease process rather than the cause of the disease. Professor Chris Ponting, and his team at the University of Edinburgh, noted these issues and secured funding for an ongoing study which hopes to start to address them – DecodeME.
DecodeME is the largest study in the world into ME/CFS, and, very importantly, is co-produced by people with lived experience of ME/CFS. The study aims to:
- Identify genes, biological pathways and cells that are directly involved in ME/CFS.
- Look at whether the genetics of ME/CFS overlaps with other diseases.
- Generate research questions that researchers can investigate in the future.
While DecodeME is an ongoing study, a paper has recently been published reporting initial findings from the questionnaire which relate to the characteristics of the people who have taken part so far and their ME/CFS.
Methods
The DecodeME study was established through collaboration between researchers and people with lived experience of ME/CFS – this collaboration has been ongoing throughout the study, and people with lived experience of ME/CFS have helped to review and develop all study documents, including the questionnaire.
The study began on 1 September 2020, with the recruitment of participants starting in January 2022. Recruitment is ongoing, and will end in August 2024.
The study is made up of two stages:
- The questionnaire, which collects information on factors including sex, age and ethnicity, and also those relating directly to ME/CFS such as type of onset, symptoms, duration, severity and responses; questions that make up the diagnostic criteria for ME/CFS: the Canadian Consensus Criteria and the Institute of Medicine (National Academy of Medicine) criteria.
- The collection of saliva samples for DNA analysis.
While everyone who agrees to take part is asked to complete the questionnaire, not everyone is asked to provide a saliva sample.
Although the DecodeME study is ongoing, this recently published paper relates to information from responses to the questionnaire between 12 September 2022 and a “data freeze” on the 19 December 2022. This data freeze did not pause the data collection, rather took a snapshot of all questionnaire responses received in this timeframe.
This recently published paper used information collected from the questionnaire to consider whether there were any differences in the population that took part in factors such as age and sex, but also in factors related specifically to ME/CFS, such as onset of disease, length of illness and severity. The authors also considered whether there are any relationships between these factors – specifically whether the characteristics of ME/CFS differ by type of onset.
Results
17,074 participants completed the questionnaire between 12 September 2022 and 19 December 2022.
In summary, the questionnaire responses showed that:
- Sex: 83.5% of the respondents were female while 16.5% were male.
- Age: Females who responded to the study were younger than males – with a median age of 49 years, compared with 52 years for males.
- Ethnicity: 96.7% of the study population self-reported their ethnicity as White.
- Onset of ME/CFS: 63.3% of participants reported an infectious onset (17.2% glandular fever, 2.2% COVID-19, and 44.1% another infection(s)), although not all of these were confirmed using a laboratory test.
- Course of ME/CFS: 58% of participants reported that their ME/CFS was fluctuating, 15.3% said their ME/CFS was getting worse, 12.7% said that it was relapsing and remitting, 8.7% said there was no change, 4.3% said that their ME/CFS was improving, and 0.7% said they were recovered.
- Duration of ME/CFS: 18.4% of participants had lived with ME/CFS for less than 5 years, 20.3% for 5–10 years and 61.3% for over 10 years, with a very small proportion of these people reporting that they were born with ME/CFS.
- Severity of ME/CFS: Using definitions of severity from the NICE criteria, 33.8% had mild ME/CFS, 53.4% had moderate ME/CFS, 12.0% had severe ME/CFS, and 0.7% had very severe ME/CFS.
- Other health conditions (comorbidities): 50.6% of participants reported that they had two or more diagnosed conditions in addition to their ME/CFS; fibromyalgia and irritable bowel syndrome (IBS) were the most common to occur together.
- Symptoms: The most commonly experienced symptom for participants in DecodeME was post-exertional malaise, followed by unrefreshing sleep, brain fog, fatigue, muscle pain and gut symptoms.
How did these factors relate to one another?
The study found that length of illness, symptoms experienced, and comorbidities differed by the type of onset of ME/CFS. These results are summarised in the table below.
| Onset of ME/CFS | Characteristics associated |
| Glandular fever infection | More likely to report: tender or swollen glands; viral infections with long recovery periods; relapsing and remitting symptoms |
| COVID-19 infection | More likely to report: having mast cell activation syndrome; a tight feeling in the chest; burning sensation in lungs |
| Another infection(s) | More likely to report: mental fatigue; viral infections with long recovery periods; shingles or symptomatic Lyme disease in the past six months Less likely to report: active clinical depression; active fibromyalgia |
| Onset not through infection | More likely to report: fatigue more than half the time; to feel nauseous; recent clinical depression symptoms |
| Do not know whether or not onset through infection | More likely to report: fibromyalgia as a comorbidity Less likely to report: cold- or flu-like symptoms; improving symptoms; relapsing or remitting symptoms |
In addition, the study found that female participants reported significantly more comorbidities and symptoms compared with males. A higher severity of ME/CFS was also associated with being female, but also: older age, longer length of illness (more than 10 years), having a comorbidity, and reporting ME/CFS to be fluctuating rather than relapsing and remitting.
Summary
The initial findings from the DecodeME questionnaire suggest that both sex and type of onset of ME/CFS are associated with the symptoms experienced, comorbidities and length of illness.
The information collected in the DecodeME questionnaire – including information relating to ME/CFS diagnosis – was reported by the participants themselves. Information collected in this way – through self-report – is limited as participants may not always be able to accurately recall information, particularly when it relates to details of events that occurred in the past. In addition, questions asked in the questionnaire may have been interpreted differently by different participants which may affect the results. Despite this, using a questionnaire has allowed the research team to reach and collect detailed information on a huge number of people with ME/CFS; this may not have been possible using other methods.
DecodeME is the first ME/CFS study with enough participants to allow a detailed statistical comparison of differences between males and females. Despite this, while the male–female split observed in the study is approximately consistent with the previously estimated 4:1 ratio (which would be 80% female and 20% male) at 83.5% female and 16.5% male, the proportion of male respondents is slightly lower than expected.
In addition, while 18.3% of the population in England and Wales identify as non-White, only 3.3% of the respondents to the DecodeME questionnaire self-reported ethnicity as non-white. This may mean that the methods used by the study have not accurately captured all minority ethnic groups. It is unclear whether or not the questionnaire was available in other languages, but translating study documents is an easy way to try to increase inclusivity.
While the DecodeME study has worked hard to provide accessible options for participation, and has captured 12.7% of people with severe and very severe ME/CFS, in reality this group is nearer 25% of all people with ME/CFS. This means that it is possible that half the people with severe and very severe ME/CFS are not represented in the findings of this early analysis. This challenge is something that ME Research UK has written about previously, and is recognised by the researchers working on DecodeME.
Despite the limitations of the information collected in the questionnaire, the DecodeME study is a hugely important step in biomedical research into ME/CFS, and the first study to gather detailed information from such a large number of people with the illness. These early findings build on existing evidence that those with ME/CFS are a diverse group, and the study has started to address the need to investigate ME/CFS in different groups, such as by sex and type of onset. It is important to remember that the results presented in this paper do not represent all the people who have taken part in the DecodeME study, rather, they reflect those who took part in the first three months of recruitment. The DecodeME study is ongoing, and there is still the opportunity to take part if you have not done so already.
Takeaway messages
- DecodeME is the largest study in the world into ME/CFS, and, very importantly, is co-produced by people with lived experience of ME/CFS.
- There are two stages to the study: a questionnaire and collection of saliva samples.
- A new paper has been published reporting initial results from the questionnaire.
- 17,074 participants completed the questionnaire between 12 September 2022 and 19 December 2022.
- Of these, 83.5% of the respondents were female while 16.5% were male.
- The study found that length of illness, symptoms experienced, and comorbidities differed by the type of onset of ME/CFS.
- Limitations of this paper include that the information collected is self-reported, and that the study population may not be completely representative particularly in relation to ethnic minority groups.
- Despite the limitations of the questionnaire, the DecodeME study is a hugely important step in biomedical research into ME/CFS, and the first study to gather detailed information from such a large number of people with the illness.
The DecodeME study is ongoing, and there is still the opportunity to take part if you have not done so already
