Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

[V.R.T.]

I'm not a sufferer so I can't really know, but none of the depression-prone people I've known and worked with ever complained about having the 'flu-like symptoms, pain, and crippling orthostatic intolerance that characterise ME/CFS. You don't tend to see them in descriptions of depression symptoms either.

Depression is multifaceted, but you'd think ME/CFS and PEM symptoms would be distinctive enough to be separated from it. Perhaps not in a single consultation with a newly ill patient bewildered by a whole array of bizarre symptoms, but that's true of many conditions.

I didn't have noticeable PEM/flueyness but I did feel quite queasy a lot of the time, feeling faint, lots of random aches and pains.

But as I said I'm not sure I had 'pure' depression so I'm probably not the best example.

 

[forestglip]

The DecodeME questionnaires are available online, here and here (@Andy I also used to be able to find them on the DecodeME website, for example here, but the links seem to have stopped working). I think it is fair to say that they've collected all the information people were asking about.

I wonder if a question about hours of time lying down would be good for future studies. I think either time lying down or step count might be the best indicators of severity we currently have (though step count is probably too difficult for people to estimate without using a tracker).

Since the hallmark feature of ME/CFS is worsened symptoms after exertion, and since body position is a form of exertion, I would expect time spent in more 'active' body positions to be a decent marker for how negatively exertion affects a given person.

Even if this is subject to issues with recall, it might lead to less heterogeneity and ambiguity than the more subjective approach of trying to fit yourself into one of these boxes:

• How severe is your illness? Please choose the group you fit most often, or that best describes how severe your illness is overall, even if the detail doesn't exactly match your experience.
  • Mild – People with mild ME/CFS care for themselves and do light domestic tasks (sometimes needing support) but may have difficulties with mobility. Most are still working or in education, but to do this they have probably stopped all leisure and social pursuits. They often have reduced hours, take days off or use the weekend to cope with the rest of the week.
  • Moderate – People with moderate ME/CFS have reduced mobility and are restricted in all activities of daily living, although they may have peaks and troughs in their level of symptoms and ability to do activities. They have usually stopped work or education, and need rest periods, often resting in the afternoon for 1 or 2 hours. Their sleep at night is generally poor quality and disturbed.
  • Severe – People with severe ME/CFS are unable to do any activity for themselves or can carry out minimal daily tasks only (such as face washing or cleaning teeth). They have severe cognitive difficulties and may depend on a wheelchair for mobility. They are often unable to leave the house or have a severe and prolonged after-effect if they do so. They may also spend most of their time in bed and are often extremely sensitive to light and sound.
  • Very severe – People with very severe ME/CFS are in bed all day and dependent on care. They need help with personal hygiene and eating and are very sensitive to sensory stimuli. Some people may not be able to swallow and may need to be tube fed.

Maybe something like:

• How many hours of the day are you in an upright position? This means total hours spent in any position other than lying down, for example all time spent sitting, standing, or walking combined.
  
  For example, if you spend every hour of the day lying down, you would answer 0 hours upright. If the number of hours is different on different days, choose a number that best represents a typical or average day. Round to the nearest whole number. If you do not know, select "Not sure".

Of course, there's a minimum response of 0 hours, which might include both severe and very severe cases. If there's a need to differentiate, maybe the subjective classification could be combined with the hour answer.

 

[Yann04]

I wonder if a question about hours of time lying down would be good for future studies. I think either time lying down or step count might be the best indicators of severity we currently have (though step count is probably too difficult for people to estimate without using a tracker).

Since the hallmark feature of ME/CFS is worsened symptoms after exertion, and since body position is a form of exertion, I would expect time spent in more 'active' body positions to be a decent marker for how negatively exertion affects a given person.

Even if this is subject to issues with recall, it might lead to less heterogeneity and ambiguity than the more subjective approach of trying to fit yourself into one of these boxes:


Maybe something like:


Of course, there's a minimum response of 0 hours, which might include both severe and very severe cases. If there's a need to differentiate, maybe the subjective classification could be combined with the hour answer.

+1

 

[OrganicChilli]

I wonder if a question about hours of time lying down would be good for future studies

I'm not sure about that. I think this will only apply to those with OI, but won't tell us much about everyone else. It can be added as an additional symptom, but it's not universal.

I can sit upright all day long, but I can't watch TV and can't walk more than 1,500 steps while I'm at home and even less if I have to leave the house.

 

[Verity]

I wonder if a question about hours of time lying down would be good for future studies. I think either time lying down or step count might be the best indicators of severity we currently have (though step count is probably too difficult for people to estimate without using a tracker).

I think this is a good idea.

I’m not sure if this only applies to me, so maybe it’s not helpful, but it might be good to word the question in a way that accounts for differences in how frequently someone has to lie down. I am moderate, and I improved substantially this year, but I would show up on your question as zero hours lying down before and after the improvement. The change in my health is obvious if you look at how frequently I lie down for short periods (usually 10 min), though. I imagine you’d get a large span of people from the mildest to moderate people who lie down multiple times a day all reporting zero hours lying down.

 

[Yann04]

I'm not sure about that. I think this will only apply to those with OI, but won't tell us much about everyone else. It can be added as an additional symptom, but it's not universal.

I can sit upright all day long, but I can't watch TV and can't walk more than 1,500 steps while I'm at home and even less if I have to leave the house.

I think for a single question its a good proxy for severity.

Nothing will be a perfect proxy. Because you can’t measure severity with a single question. But I think estimate of hours laying down is not a bad one. Obviously your situation shows why it’s not perfect. But I don’t think that discounts it,

Like it’ll give you pretty perfect seperation between very severe and moderate people to sort by hours laying down. I don’t think many other single questions can do that. (step count is too unreliable to be done without objective measuring so can’t just ask).

 

[OrganicChilli]

step count is too unreliable to be done without objective measuring so can’t just ask

But the same goes for time spent laying down, doesn't it? Eg @Verity needs to add up their 10 min rest periods.

 

[forestglip]

But the same goes for time spent laying down, doesn't it? Eg @Verity needs to add up their 10 min rest periods.

I think most people could estimate hours upright to within about 2 hours. For step count, I personally have almost zero idea how many exact steps I walk. Whenever I try a tracker, I'm surprised by how many steps there are in a short walk around the house.

 

[forestglip]

I am moderate, and I improved substantially this year, but I would show up on your question as zero hours lying down before and after the improvement. The change in my health is obvious if you look at how frequently I lie down for short periods (usually 10 min), though. I imagine you’d get a large span of people from the mildest to moderate people who lie down multiple times a day all reporting zero hours lying down.

I think this might be backwards from what I said. Since lying down includes sleeping, I thought it'd be too much math to try to add up time spent lying down while sleeping plus throughout the day. So instead it's time spent not lying down.

So if you are mostly up from when you wake up at 8 AM until you lie down for bed at 10 PM, that's 14 hours. And if you normally do about ten short lie downs of 10 minutes each, maybe you could subtract one or two hours from that.

 

[Kitty]

I can sit upright all day long, but I can't watch TV and can't walk more than 1,500 steps while I'm at home and even less if I have to leave the house.

Same, I only ever lie down if I'm ill or need to sleep because it's too painful. On average I have my feet on the floor about 16 hours a day, so if that were the principal measure it would give a totally inaccurate picture.

But if the measures included distance that can be walked without stopping for a rest/triggering PEM (about 20 metres) and time I'm able to stand on the spot before I feel ill (a minute at best), it would balance it out by capturing other important facets.

 

[OrganicChilli]

distance that can be walked without stopping

Yes, this is so much better than pure step count! And it's also why I can walk much more when I'm at home because I only walk short distances. But 500 steps all at once even if it's the only walking I do in a day? That's going to give me PEM. Especially because I used to be a fast walker so I really have to force myself to slow down.

 

[Utsikt]

Yes, this is so much better than pure step count! And it's also why I can walk much more when I'm at home because I only walk short distances. But 500 steps all at once even if it's the only walking I do in a day? That's going to give me PEM. Especially because I used to be a fast walker so I really have to force myself to slow down.

Maybe worded like

What’s the longest distance you can consistently walk in one go during a normal day?​

 

[OrganicChilli]

Maybe worded like

What’s the longest distance you can consistently walk in one go during a normal day?​

Yes and I think this is a fairly standard question for disability benefits assessments actually. Here in the UK it's less than 20m, less than 50m or less than 200m if I recall correctly. But for our purposes something open ended is better.

 

[Kitty]

Yes and I think this is a fairly standard question for disability benefits assessments actually

I think the concepts used in UK PIP assessments could potentially be useful tool in things like this.

The questions don't simply ask whether you can do something, but whether you can do it safely, as often as you need to, and without consequences (pain, fatigue, aggravation of your illness) that could prevent you doing other essential activities. It's pretty good at revealing the true level of disability.

 

[Verity]

I think this might be backwards from what I said. Since lying down includes sleeping, I thought it'd be too much math to try to add up time spent lying down while sleeping plus throughout the day. So instead it's time spent not lying down.

So if you are mostly up from when you wake up at 8 AM until you lie down for bed at 10 PM, that's 14 hours. And if you normally do about ten short lie downs of 10 minutes each, maybe you could subtract one or two hours from that.

I think I have lost the thread of this a bit due to brain fog, sorry haha. What I was trying to get across was just that if we’re reporting using hours, some of us might look very similar to each other when we are actually not as much. For example, days where I’m upright for 14 hours and days where I’m upright for 13.5 hours are actually very different in terms of level of function, and whether they look different on paper would just depend on whether someone rounds up or down.

But I think the idea was to use step count as well, which might eliminate that problem. My step count would probably be very different even if my hours upright weren’t.

And also this might just be a me problem. I get the impression most people’s good vs. bad days have much larger differences than mine.

Sorry if I’ve confused this! Probably best to ignore me here…

 

[forestglip]

I think I have lost the thread of this a bit due to brain fog, sorry haha. What I was trying to get across was just that if we’re reporting using hours, some of us might look very similar to each other when we are actually not as much. For example, days where I’m upright for 14 hours and days where I’m upright for 13.5 hours are actually very different in terms of level of function, and whether they look different on paper would just depend on whether I round up or down.

Yeah, my assumption of how well it would match severity was not based on much data. Just some anecdotes on the forum and knowing that severe/very severe people are known for spending virtually all time lying down. And for myself as probably moderate, I spend most of the time lying down, but I still spend about 3 or 4 hours upright. Maybe it's not quite a one to one relationship for hours to severity for all severity levels or in everyone.

But I think the idea was to use step count as well, which might eliminate that problem. My step count would probably be very different even if my hours upright weren’t.

I was just thinking this would be doable for cohorts of thousands of people like DecodeME where you can only ask questions and not actually measure something like steps easily.

 

[Verity]

I was just thinking this would be doable for cohorts of thousands of people like DecodeME where you can only ask questions and not actually measure something like steps easily.

It may well work! I might be a major outlier, anyway, being upright this much but nearly housebound…