SequenceME genetic study - from Oxford Nanopore Technologies, the University of Edinburgh and Action for ME

[Jonathan Edwards]

How confident we are that ME/CFS has a strictly infectious origin ?

We aren't. Moreover the crucial importance of genetics in diseases of infectious origin is known by every medical student. Reiter's syndrome is the paradigm - very strongly predisposed to by HLA-B27. Then there is mannose binding protein deficiency and staph problems, HLA-DQ and post-influenza narcolepsy, lysosomal gene defects and chronic granulomatous disease and no doubt rheumatic fever and post-streptococal glomerulonephritis have genetic predispositions...

 

[V.R.T.]

HLA-DQ and post-influenza narcolepsy,

This would perhaps be an interesting connection to some of the things we've discussed recently but I assume the HLA DQ link didn't stand up in the separate analysis from what Chris apparently said at the Berlin conference.

 

[Jonathan Edwards]

I assume the HLA DQ link didn't stand up in the separate analysis from what Chris apparently said at the Berlin conference.

The HLA-DQ link was very weak compared to narcolepsy anyway. I was a bit surprised that Chris said that nothing came up on HLA at all. I thought that even with correction there was a weak DQ signal, but DQ is notorious for being misleading at this sort of level so that story probably doesn't not take us anywhere, sadly.

 

[Andy]

Can meaningful analysis be done on 6,000 samples? If for some stupid reason we can’t get the additional 3,000 funded

Yes, absolutely, and is why our hope is for analysis of those samples to be the next step forward.

In terms of costs for future phases, I'm afraid we don't currently have figures that we would want to release for each individual phase. I understand the interest though, and will see if we can come up with our best estimate for each phase.

 

[Andy]

Do you know if the MEA has been approached to ask if it would be willing to contribute to Sequence?

All I will say is that we are exploring many potential funding sources.

Is there any particular or new criteria for which samples will be used?

If you mean the ME/CFS samples, then they are samples from DecodeME, which used CCC and/or IOM selection criteria. If you mean the LC samples, then the inclusion criteria is yet to be decided. Pasting in an earlier answer I gave to the question of the LC selection critieria,

The definition is yet to be decided upon and forms part of the work already funded by previous supporters. I can't guarantee at this stage what the definition will be but we are well aware that it will need to be better than anything as vague as "3 months of any symptom at all after a Covid infection". Given that eventually we will be comparing them with DecodeME particpants I personally would like to see all LC participants evaluated with the DecodeME questionnaire for likely ME/CFS status.

 

[PeterW]

But I cannot suppress my contrarian streak: There is part of me that is skeptical of genetics being especially important in infectious-origin diseases.

It's a bit like trying to understand the plot of Midsomer Murders by looking at the blueprint of the Samsung TV.

Tonsillitis is infectious in origin, but recurrent tonsillitis has a significant genetic predisposition: link to paper here