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Can these SNPs be replicated? The answer is "no". I went back to the UK Biobank CFS findings (far more than 305 ME/CFS patients) and asked what is the association (what are the p-values?) of these SNPs to CFS status? The answers are: p = 0.43, 0.41, 0.56, 0.92 and 0.17. None of the 5 are...

Small study, but great to see a genetic signal. This needs replication and more samples, but at the moment this does point towards an adaptive immune contribution to ME. Encouraging. Mod note: Post copied to Human Leukocyte Antigen alleles study Human Leukocyte Antigen alleles associated with...

comment copied from Genome-wide association study thread Small study, but great to see a genetic signal. This needs replication and more samples, but at the moment this does point towards an adaptive immune contribution to ME. Encouraging.

Yes, this is true. I am hoping (not expecting!) that the GWAS is funded and that a funded PhD student picks the study. If the GWAS is not funded and a funded PhD student picks the study then - not optimal - we will carry on anyway using available UK Biobank data (on CFS not ME). If the GWAS is...

Thanks. What other optional questionnaires would you like to see? SF-36, for example? Yes, we need to ensure that the questionnaire load for a person with ME/CFS is not too great.

If there is a compelling argument for such a trial (passed by an ethics committee) then eventually yes, but more likely (and sooner) we expect researchers interested in epidemiology, genetics, molecules ('omics), diagnostic criteria and physiological responses to take advantage of the...

Yes, the idea is that the 20,000 cohort would be recontactable for further questionnaires and studies - no obligation to participate! All data would be anonymised but bona fide researchers would apply for access to the data. Note that all genetic/questionnaire/biomedical data would be linked to...

Thank you all for this fantastic feedback - keep it coming. I really like the way that the conversations we've been having recently within the Partnership are exactly the ones you've laid out in this thread, but also that there is a flow of ideas and info in both directions. Happy Christmas/New...

Thanks for this. Just to mention that the MRC's emphasis on a GWAS is not new, and goes back to their Strategy Board's comments (25 March 2019) when they said: "Overall, the Genome Wide Association Study (GWAS) component of the study was considered to be a good agnostic starting point and...

Hi. For information, I had only a minor role in MEGA. There were no posts and no funds proposed to come to my team. I wasn't down to do the GWAS - I think Bristol was going to do that. The biggest difference between this GWAS and MEGA's are in the recruitment strategies: via clinics versus...

Thank you so much for your comments. As to your last comment/question, the MRC and NIHR are very serious that pwME/patients are front-and-centre of this project proposal. The NIHR correctly insists that we have a patient-public involvement strand running through the project where, importantly...

Interesting! I met with a PR agency last week and they said that the greatest impact would come from telling the stories of people with ME. Far better for the public to be confronted by a person who has lived experience than a scientist who is usually thought of as being dispassionate/objective.

Yes, we will take care to investigate age-related stratification, particularly because our primary cohort (UK Biobank) is of older folk. One of the covariates used in our analysis is age too.

We are going to look computationally to see whether genetic signals for diagnosed ME/CFS are shared with those for other traits using LD score regression. We hope to be able to find genetic signals that are only ever seen for ME/CFS and not for other inherited traits.

"the study wants to study every single person with ME/CFS in the UK above 18". I like this idea! Thanks.

Yes, this is correct. Initially, for controls we will use the 500,000-strong UK Biobank study (not to be confused with the ME Biobank at the LSHTM).

Yes, we are going to ask participants to consent to be recalled into new studies. This provides the exciting prospect of "recall-by-genotype" studies, and for the UKMEB to target individuals for blood samples that would be particularly informative. Importantly, the funds that we are applying for...

One of our inspirations is the “snowball sampling” spit-and-post approach of Genes for Good project (https://genesforgood.sph.umich.edu/) in the USA which uses social media to engage a large, diverse participant pool in genetics research and education.

Thanks. Yes, we've been discussing a multi-stage process, with the first step being in the UK. Standard GWAS analysis takes account of population stratification, but I agree that we need to take care of residual bias and think about exploiting multiple different control cohorts. We plan to use...

When we discussed this as a team, we thought that the only limit (because of consent issues) was the lower limit of 18 years, but we were not going to apply an upper age threshold. So: you'd be welcome to participate (if we are funded)...!