ME Genetics Research Symposium, Edinburgh, 14th September 2022

Andy

Andy

Senior Member (Voting rights)
** Early details, more will come closer to the date **

Action for M.E. and the MRC Human Genetics Unit, University of Edinburgh are holding a genetics research symposium on 14th September 2022, at the University of Edinburgh.

This will be a hybrid option for those that would prefer/are unable to travel. The event is open to anyone who wishes to attend but we hope to have a good mix of researchers, people with lived experience of ME and anyone with a personal or professional interest.

There will be a mixture of presentations and a workshop during the day.

No registration available at time of posting (will presumably follow).
 
M.E. Genetics Research Symposium for Researchers, Carers and People with ME

About this event

Join us to help accelerate genetic research into Myalgic Encephalomyelitis (ME/CFS).

Action for M.E. and the University of Edinburgh Human Genetics Unit are delighted to invite you to the M.E. Genetics Research Symposium on 14 September 2022 in Edinburgh.

The symposium will bring together researchers interested in ME, people with ME, carers and potential funders to drive collaboration in this field and develop a 10 year programme of ME/CFS genetics research. The summit is open to anyone who would like to join us and is available at no cost. Adjacent quiet rooms are available for use throughout the day.

The event will be hybrid and you are welcome to join in person or remotely. Please see the programme for the day below.

Thank you for your interest in the event and we look forward to hopefully seeing you online or in person on the day.

Sonya Chowdhury (Chief Executive, Action for M.E.) & Prof Chris Ponting (Investigator, MRC Human Genetics Unit)


PROGRAMME - S1.14 South Seminar Room

09.45 Registration

10.00 The Centre of Excellence vision, Prof Chris Ponting, Group Leader, MRC Human Genetics Unit, University of Edinburgh

10.10 The Power of Patient and Public Involvement (PPI): Sian Leary and Andy Devereux-Cooke, DecodeME PPI

10.30 Title TBC: Marte Viken, Researcher, Oslo University Hospital

11.10 BREAK (refreshments will be provided for people attending in person)

11.30 Post-exertional malaise as a Chronic Ischaemia-Reperfusion injury in Long COVID and ME/CFS resulting from fibrin amyloid microclots: Prof Douglas Kell, Research Chair in Systems Biology, University of Liverpool

12.10 Dr Kenny Baillie, Snr Clinical Research Fellow in Anaesthesia & Critical Care, University of Edinburgh

12.50 Title TBC: Steve Gardner, CEO, PrecisionLife Ltd


13.30 LUNCH (lunch will be provided for people attending in person)


14.30 Workshops:

• What would a 10-year programme of ME/CFS genetics research and follow up studies look like? How can we drive it forward?

• How can we forge collaborative links with researchers who are not currently active in ME/CFS research?

• How do we ensure PPI is at the heart of future genetics research?

15.30 Plenary - feedback from workshops: Sonya Chowdhury, CEO, Action for M.E.

16.00 Close

Register at https://www.eventbrite.co.uk/e/me-genetics-research-symposium-tickets-388051862567
 
Andy said:
10.10 The Power of Patient and Public Involvement (PPI): Sian Leary and Andy Devereux-Cooke, DecodeME PPI
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I'm sorry to disappoint what, in my mind at least, must be hordes of people who were looking forward to seeing me, as post-covid I'm not well enough to take part. At the moment I think Sian will still present this, and if she can then I'm sure she'll do a better job without me.
 
Trish said:
I hate to be picky but - 2 mistakes in the first paragraph. DeCodeME should be DecodeME and it's Prof Chris Ponting, not Pointing.
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It's correct in the next mention, "DecodeME" but continues to be "Pointing" until the last mention in the article where it is corrected to "Ponting".

"A significant portion of the day was given over to discussion about the role of patient-priority-partnerships and involvement (so-called PPI)". Not quite, PPI is Patient and Public Involvement, the standards for which can be found here, https://sites.google.com/nihr.ac.uk/pi-standards/standards, while priority setting partnerships are an example of PPI.
 
I was able to watch most of this webinar and took some notes - my handwriting is atrocious however so I am struggling to properly decipher some, so there may be some things not quite right. It might highlight things to look for when the videos/ recordings are made available

HLA study - Marte Viken
Study set up to test hypothesis that ME/CFS is an immune mediated disease. Blood samples collected from different sources (hence good representation of severely affected) and yielded serum, plasma and DNA
Molecular study using a detailed sequencing process that found 4 HLA alleles with association, 2 positive arousal(?) signals. Signals for TPPP
SNPs had no genome wide significance, conditionary analysis found class I and Class II as being independent. Allele DOB1*03:03 of interest - codes in regulation of aspartic acid
I've noted that in the cyclophosmanide study responders - 83% of responders carried risk alleles (could this relate to sub group?)

Microclots - D. Kell
Inflammation at core, some effects become causes due to feedback loops (I've noted collagen for some reason). Pre COVID (2016), LPS impact on clots - very different from normal clotting. Increased formation of B (as in beta) sheets from tiny amount of LPS; more resistant to fibrinolysis (as amaloid). Failed fibrogin(olysis?) = hypoxia

ME/CFS - more thrombin clots, area taken up microclots x10 greater in ME/CFS. Tissues - capillaries similar size to microclots
Ischemia - chronic reperfusion injury- lactate / ROS - Superoxide & peroxide in presence of iron - Fenton/ Haber Weiss reactions. Catalytic action - hydroxyl ions and oxidative stress. iron liberated can wake up bacteria and virus that are dormant.
In Long Covid, hyperactivation of platelets causes/ drives clotting.
ROS sequelae (nitrotyrosine, alpha(?)-OH-guanine, malondialdehyde) _ inference not good
proposal is PEM as cell death kinetics - which may explain delayed nature

Microclots = chronic version of reperfusion injury

Kenny Baillie (criitical care/ anaesthesia specislist )
Public engagement via charity run by relatives of those with sepsis. Search showed that despite 121 trials and multi millions in funding, biology of sepsis not fully understood. COVID prompted look at genetics and found that single amino acid changes in IFN10 (interferon) and DC SCR1 lead to broken protein = changes in function/ effect = greater disease. IFNAR2 broken molecules.
Critical illness with COVID is second stage of illness (in COVID is steroid response so this is inflammation) Acute subsets have strong signal, more type 2 signalling harmful= greater effect of COVID. Scientific method used .

Steve Gardner - Precision Life
Combinational analysis of multi modal data. ME/CFS dataset - all patients had 3 SNPs in combination (?) 95% non coding. 9 in coding, no SNPs in linkage dysregulation, 25 critical SNPs, - 14 prioritized genes. Less than 20% patient overlap between groups, 15 correlates? with pain questionnaire
Key areas/ groups -
autoimmune genes SLC15A4-( SNP ID rs 22398428), TME232 ( SNP ID rs58264436), GPC5 (SNP ID rs16947234), PHACTR2 ( SNP ID rs 9403525)
metabolic genes ATP9A (SNP ID rs2904106), KCNB1 (SNP ID rs 237475), AKAP1 (SNP ID rs 3785477), CDON (SNP ID rs73021223), INSR (SNP ID rs59165976)
sleep disturbance, CLOCK (SNP ID rs6832769), SCLA6A11 (SNP ID rs2304725)
host response, S100PBP (SNP ID rs41306603), USP6NL (SNP ID rs2499908), SULF2 (SNP ID rs56218501)
Group9 - AKAP 1 maps & regulates mitochondrial response via AMPK. Group 15 SLC6A11 & GAT 3 - GABA reuptake - neuro cognitive elements. CLOCK rs6832769 more likely to have fibromyalgia diagnosis as well.
Use of data - can be of use to repurpose drugs.

Workshops - Chris Ponting's workshop focused on how to build a team for genetic research - wide team membership (across disciplines) and cooperation was felt to be key to progressing meaningfully. Looked at how genetic research could " mesh" with the priorities of the PSP.
Highlighted difficulty of consistency for samples - diagnosis/ source of samples
would stratification reduce validation between individuals?
research could use-
cell based
blood based
use of animal models - good if you know what to look for but human/ animal validity issues
omics technoligies, small or large sacle but effects may be downstream rather than causal.
questionnaires -good for use with quantative datasets
active monitoring - cheap, mature technology - could be useful for stratification?
 
Andy said:
I'm sorry to disappoint what, in my mind at least, must be hordes of people who were looking forward to seeing me, as post-covid I'm not well enough to take part.
Click to expand...

Sorry to hear you have not been well after covid. I hope you are improving and that it's not too bad. Love :heart:

This event looks really interesting; I look forward to any uploaded videos. Thanks to all who organized it and took part.
 
Andy said:
Part two of ME Research UK's coverage, https://www.meresearch.org.uk/genetics-research-symposium-part-2/
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ADDED I wasn't at the meeting, but a lot of this reads like a general commentary on genetics research from the author, not reporting/a summary of the genetic section of the symposium (for instance, I'd be surprised if any of the speakers spent much time on the 2007 Kerr study).

"It is important to note that the term ‘association’ does not necessarily mean there is a causal relationship, only that some SNPs have been identified that may be involved and that require more research."
That's not wholly accurate. The whole point of DNA studies is that if there is an association, it indicates a causal relationship. But not necessarily with the SNP's identified (too complex to explain here). It's also possible any associations are artefacts (also complex to explain). And it's quite right to say more research is needed to investigate any promising findings.
 
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