Simon M
Senior Member (Voting Rights)
ME/CFS onset had two peaks, which may be a clue to causes
New blog. (Formatted paper. Thread)A new study strengthens the findings that ME/CFS is a disease with a highly unusual feature. Analysis of survey data on patients across Europe found there are two peak ages for
getting ME/CFS, around 16 and the late 30s – a rare bimodal pattern. There are differences between people in the two peaks. Those in the early peak are more likely to report an infectious onset, be more severely ill, and have close relatives with ME/CFS. That combination of age peaks is unique, even amongst those diseases that do have two peaks, and this could be a clue to the biology behind ME/CFS
The biology of ME/CFS is hard to pin down, with few unique features. But a 2014 study of medical records in Norway suggested a striking one: two different ages when people are most likely to get ill. Two onset age-peaks is unusual in disease biology, but it is seen in a few cancers and some autoimmune diseases.
It started with a tweet
This unusual pattern seemed to me back then as though it might help unravel the biology behind ME/CFS, but, over the years, the clue wasn’t pursued. Perhaps no one thought the finding was real: the study was limited to one country, and data were for age at diagnosis – which can be very different from age at onset.
Last year, I decided to see if we could get stronger evidence by focusing on age at onset rather than diagnosis, and by looking in more countries. An initial trawl of data sources found nothing, so I tweeted to ask if anyone had something like this. And struck gold.
Trude Schei, Head of the ME Norwegian ME Association, replied to say that she had led the 2021 European ME Association (EMEA) survey, and had a database of over 10,000 responses with onset age, year, suspected trigger and other invaluable data from countries across Europe. She and her co-lead, Professor Arild Angelsen, were willing to share the data. Suddenly, a study was on.
We formed a team consisting mostly of people who live with ME/CFS: having it, or being close to someone who does. Dr Audrey Ryback at the University of Edinburgh led the study, joined by Charlie Hillier, a scientist with severe ME/CFS, along with Dr Joshua Dibble, also based at the University of Edinburgh, Schei, Angelsen and myself.
Two onset age peaks
We looked at ten European countries with the largest number of responses to provide us with enough data to get a reliable picture from each country. One third of the 9,380 responses came from Norway, which had the largest number of responses by far, and for Norway two age peaks were visible with the naked eye:
For all other countries – both combined (shown above) and individually – the two peaks were less obvious and we turned to statistical techniques to robustly identify whether there were peaks in the data.
First we used a ‘dip’ test, which tells us whether we have evidence for more than one peak in our data. This produced results for Norway and all other countries combined that were highly significant, both having a p value well below the statistical significance threshold of p ≤ 0.05, at p < 0.0000000000000002 (that is, p < 2 x10-16).
Six of the nine other countries were also individually statistically significant, though Switzerland and France (which had the smallest sample sizes), and the Netherlands, were not.
Next we wanted to work out where the peaks were and describe their features. We used a technique called a Gaussian Mixture Model to do this, and the results were striking, as you can see below.
read the full blog
