UK Genome Wide Association Study (GWAS) project - draft website goes live, feedback sought on recruitment plan, and updates

Andy said:
One sentence 'lay persons' answer.

There are 3 billion DNA letters in a person's genome. The WGS would read all of those letters, while the GWAS would ‘only' read 1 million letters.
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Just to expand on that lay answer slightly (covered in the technical answer that followed):

Whole genome sequencing reads all 3 billion DNA letters, as the name implies. GWAS reads only around a million letters (one out of every 3,000 letters), but these are the letters that most frequently differ between people and so captures most of the variation between people.

GWAS is also more than 100 times cheaper than WGS - so researchers can afford to run big enough studies to produce reliable resuts.

On the other hand, WGS can also detect rare differences (too rare for GWAS to find) that make a very big difference to function, such as disabling a gene. Most of the differences detected by GWAS are subtle, modifiying (by a small amount) the level of activity of a gene.
 
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Andy said:
Analysis of the data from a GWAS is a statistical test of whether a DNA variant predicts well whether someone is either a case or a control (i.e. is the variant associated with either being a case or a control). The probability statistic (p-value) from a GWAS gives an indication of whether this variant distinguishes case vs control and because millions of places in the genome are being tested at once, the multiple testing burden means that – to be truly genome-wide significant – the p-value has to be tiny, less than 5x10-8.

ETA: Slight edit to text. Removed "The “A” in GWAS is “analysis”. This" and added "of the data from a GWAS" and "(i.e. is the variant associated with either being a case or a control)".
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Edited this paragraph as described.
 
Simon M said:
Just to expand on that lay answer slightly (covered in the technical answer that followed):

Whole genome sequencing reads all 3 billion DNA letters, as the name implies. GWAS reads only around a million letters (one out of every 3,000 letters), but these are the letters that most frequently differ between people and so captures most of the variation between people.

GWAS is also more than 100 times cheaper than WGS - so researchers can afford to run big enough studies to produce reliable resuts. On the other hand, WGS can detect rare differences (too rare for GWAS to find) that make a very big difference to function, such as disabling a gene. Most of the differences detected by GWAS are subtle, modifiying (by a small amount) the level of activity of a gene.
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Yeah, I may steal that for the website.... ;)
 
Thought I would provide an update on the main queries that have been raised here that I fed back to the team. As I'm sure you will understand, we have had an incredibly busy period finalising and submitting the application, and as we did that the Covid-19 situation blew up, which has meant major disruption - mainly for our CureME colleagues but obviously affecting us all. In short, this means that I have some answers and some outstanding questions.

1. Why can’t the IOM/NAM and CCC criteria be applied retrospectively, so that it is possible to include those who now consider themselves recovered, as there won’t have been a change in their genetic information?

Discussion still ongoing on this point.

2. Why can’t the results from commercial genetic tests be used?

The technology that a participant’s DNA genotype is read out by needs to match as closely as possible with how genotypes of controls have been generated (for free) by the UK Biobank. Reading out DNA in a different way, such as using a commercial provider, will introduce unwanted biases and potentially lead to false conclusions. Using commercial genetic tests would also require us to develop systems for importing and quality controlling commercial genotypes, which would not be a good use of our resources.

3. Concerns about length and number of questionnaires. What questionnaires we will be using and why.

Discussion still ongoing.

4. Re-contactable cohort. Various concerns have been raised about other researchers being able to contact those people who sign up and/or are participants in the GWAS. An explanation of how this will work in principle is needed, including what contact information will be shared.

Re-contact procedures will match, as far as possible, those that have been in use by the UK Biobank for many years (details here). In short, participation will be entirely voluntary. Any initial re-contact would be undertaken by the MEBiomed Partnership. Decisions on whether re-contact is appropriate would be made by us with advice from the Scientific Advisory Board and subject to separate ethics approval. Re-contact will be monitored to ensure that participants are not over-burdened. Re-contact will be to establish whether (or not) participants are willing to take part in a third party research project.

5. Can we integrate a map of the UK into the website, showing numbers of participants in different regions over time?

We are in favour of this idea and will implement it if possible, while preserving participants privacy sufficiently - this has been done internally for the VIKING II GWAS project to inform their recruitment efforts and so we will engage with their team to draw on their experience.

If you feel that I have missed, or misunderstood, an important query or issue with the proposed project then let me know in a comment below.

ETA: Few minor words added/changed to improve readability.
 
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At the start of ME Awareness Week, we would like to extend our best wishes to all members of the ME/CFS community.

We had hoped that, by this time, we could have brought you some news regarding our application for funding for our proposed GWAS project but, like so many things recently, the processing of our application has been delayed due to the impact of the current pandemic.

While we wait, we are not idle. We continue to plan ahead with the hope that we will receive the necessary funding and, of course, many of our team are already involved in other research into ME/CFS and their efforts continue.

Once we have an update on the funding progress we will bring this to you as soon as we possibly can.
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https://www.facebook.com/mebiomed/posts/181099940013550




 
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