MEGA blog: Chris Ponting on Genomics "defining the molecular pathology of CFS/ME"

[eafw]

scientists new to ME may not actually know whether or not they have been adequately informed

Yes, that's correct, but that's not the main point of the question. Rather it's sowing a seed, and the way they answer will be instructive in and of itself. It also sends a message to other members of MEGA who will be monitoring these conversations. We know what they're up to.

 

[Simon]

It makes me wonder why we need 12000 patients in the ME study. Could it be perhaps because of the determination of Crawley et al to make it a fatigue study, so the numbers have to be huge so that by chance a few might actually have ME.

The answer was in Chris Ponting's statement: the effect was unusually large in the obesity study (1,900 +3,750 patient), bigger studies are needed to pick up smaller genetic effects (which are much more common, but still valuable)

One study used 1,924 type 2 diabetes patients, and then a further 3,757 patients for replication, to find that if someone has two copies of a DNA change then they weigh – on average – 3 kg more (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646098/).

A detailed ‘omics study showed that this is likely due to altered regulation of heat generation in fat cells (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1502214). This is a large effect; for a smaller effect to be detected more individuals in the cohort would have been needed

 

[Simon]

Surely, apart from the more severely ill, housebound and those who don't have an ME/CFS clinic in their area (or country in the case of Wales), it will also exclude the long term ill who may have been to a clinic many years ago, but no longer bother, or have been discharged.

The sort of patients they will be recruiting will be short term, mild patients who live in certain areas of the UK and feel disposed to bother going to a 'Fatigue/CFS clinic'.

Not helpful IMHO

Can we keep this thread on topic ie discussing Chris Ponting's blog and Q&A, as opposed to the various comments more generally criticisingn MEGA? There are plenty of other threads for that. Thanks.
[Btw, I addressed several of the above points here, on a differnt thread]

 

[Cinders66]

The answer was in Chris Ponting's statement: the effect was unusually large in the obesity study (1,900 +3,750 patient), bigger studies are needed to pick up smaller genetic effects (which are much more common, but still valuable)

Simon do you know how the figures are thought to be being planned out then ? Coming up with 12 000 sounds like a calculatuon went in. ..How many of the 10, 000 adults are going to have ME , how many severe ME, how many CFS, will some be just fatigue and what about the rest? Will it just be healthy controls? Thanks

 

[justy]

Can we keep this thread on topic ie discussing Chris Ponting's blog and Q&A, as opposed to the various comments more generally criticisingn MEGA? There are plenty of other threads for that. Thanks.
[Btw, I addressed several of the above points here, on a differnt thread]

Sorry Simon - knew I was off topic, but find it hard to keep all the different threads to mind and or to remember what I wanted to say (which is often not much).

 

[Simon]

Simon do you know how the figures are thought to be being planned out then ? Coming up with 12 000 sounds like a calculatuon went in. ..How many of the 10, 000 adults are going to have ME , how many severe ME, how many CFS, will some be just fatigue and what about the rest? Will it just be healthy controls? Thanks

Here's Chris Ponting's answer to another question

Is this study viable at 12k patients and given the heterogeneity? We do not know – which is why the results of this research are needed. We could go round-and-round on this issue, but until we have data/evidence no-one will know. CFE/ME may present clinically in a heterogeneous manner, but this might belie a less heterogeneous set of genetic contributions.

For example, are adult and adolescent CFS/ME the same or different? My guess is somewhere in between and, if so, understanding one will help to understand the other. Even if a 12k study does not produce clear results, when combined with other studies’ results (e.g. from the USA), it might yet. I think it worthwhile to attempt this study: scientifically it is the right thing to do next, although as with any study there is no guarantee of success

So you never know for sure (it depends on how big an effect there is, which you can't know without doing the study): I think an even bigger sample would be ideal (as for just about every genomics study). It's never an exact calculation.

Similarly, Chris said he doesn't think the severity is an issue, based on other genomics studies for other illnesses (for genomics specifically, it may be much more important eg for metabolomics or proteomics, where severity would have a more obvious impact).

Similarly, he made the point, in response to Julie Rehmeyer's question, that he thinks having most patients have PEM is important, to make the core patient sample as big as possible. Sorry, can't find all the quotes right now (they will be on the blog) and I'd done for the day.