Support Health Rising’s quickie Summer Donation Drive



Click here for more


“Barely slept last night after we announced funding for a £3.2m DNA study partnership that I Chair. Seven years+ of advocacy and lobbying final paid off.” Sonya Chowdhury, CEO of Action for ME – a leader in the effort

When the Brits do it, sometimes they really do it. In 2005, they ladled out 5 million pounds for the largest and still the single most expensive study ever done in chronic fatigue syndrome (ME/CFS) – the notorious PACE trial. That, as we all know, didn’t turn out so well.

The biggest ME/CFS genetic study ever seeks to provide clues to the cause of the disease.

Fifteen years after the Brits funded the biggest ME/CFS clinical trial, they funded the largest and one of the most expensive ME/CFS studies ever: a  $3.2 million pound ($4 million dollar) 20,000 person, 4-year genetic study.

As good as this study is, the willingness of the U.K. funders to plop down an large amount of money on a biological study for ME/CFS might be the most important takeaway.

Simon McGrath, in his blog “UK spends £3 million on the world’s biggest ME/CFS study“, pointed out that of the two funders of the study, the Medical Research Council (MRC) has only funded a few fairly small biomedical studies in ME/CFS before, and the National Institute of Health Research has never funded any.

Things can change – even in the U.K.

“As someone living with ME/CFS, I’m well aware that the patient community has waited a long time for a study such as this one that has such a strong, genuine element of patient involvement. All of us involved with this research project hope that it can start to address the totally unwarranted stigma and lack of understanding that so many patients with ME/CFS face on a daily basis.” Andy Devereux-Cooke

It also bears noticing that the London Times article on the study spent a significant amount of print on the relationship between COVID-19 and ME/CFS. The COVID-19 pandemic has the potential to forever change how people think about ME/CFS and there are signs that it already is. (Stay tuned for a blog on that coming up.)

The Study

The 20,000 person GWAS, or Genome-Wide Association Study, is a basic, ‘get down to the bones of our DNA’ study. The goal is to find single nucleotide polymorphisms (SNPs) – small changes in the genetic makeup of genes – which can change their functionality and contribute to ME/CFS.

The beauty of the whole genome approach being taken is its openness. Instead of guessing which genes are involved – guesses which Francis Collins pointed out (see below) have been more often than not wrong – they look at all the genes. Collins, the master communicator that he is, explains the promise of GWAS studies well.

“GWAS, or Genome-Wide Association Studies, are responsible for the deluge of discoveries in terms of the genetic risk factors for common disease that have been pouring out of research labs recently … if you’re successful…it allows you to zero in on a place in the genome that must be involved in disease risk without having to guess ahead of time what kind of gene you’re going to find.


The beauty of GWAS is it got us past the candidate gene approach, which had been pretty frustrating because most of the candidates turned out not to be right, to be able to say the whole set of genes are your candidates, let’s consider all of them, and here’s a strategy that’s comprehensive enough to allow you to do that.” Francis S. Collins, M.D., Ph.D.

That inclusivity has lead GWAS studies to become known for the sometimes weird, but  deeply informative, results that have popped out.

The very first GWAS study done back in 2005 on macular degeneration identified 2 SNPs in genes encoding complement factors in the immune system which weren’t even remotely on anyone’s radar. In fact, the complement system was so off the charts in macular degeneration that complement research struggled to gain a foothold. Since then, though, two more complement genes have been identified, and drug development is under way.

A GWAS study uncovered the totally unexpected link between blood type and the risk for severe COVID-19 illness.

GWAS Studies: the Pluses and Minuses

“At every fork in the road … your genome has its thumb on the scales, making it slightly more likely that you will develop in one direction or another.” Eric Turkheimer, a behavioral geneticist

Fifteen years and about 4,000 GWAS studies later, we know a lot more about what GWAS studies can and can’t do. A recent review, “Benefits and limitations of genome-wide association studies” concluded that GWAS studies have “successfully identified risk loci for a vast number of diseases and traits”.

GWAS Plus’s and Minuses

They’ve also often implicated “genes of unknown function or of previously unsuspected relevance” which after further study, have uncovered “novel biological mechanisms”.  The data gained from GWAS studies can also form the basis for numerous other genetic studies.

While GWAS studies can provide incredible insights they tend to find gene variants that account for only a modest proportion of the heritability of complex traits. One reason for this is that it’s just very hard to identify some types of variants (common variants with very small effects, rare variants with small effects, ultra-rare variants) which, when they are all added up together, can significantly contribute to heritability.

Many traits in the body are polygenic; i.e. they arise from the interactions of many  genes. While it would be nice, indeed, to highlight one or two or three genes that have turned the tables on people with ME/CFS, that’s not likely to happen.  Instead of pointing to X gene causing a disease, GWAS studies tend to uncover arrays of genes and biological pathways that merit further study; i.e. they’re more likely to point fingers rather than directly pinpoint causes.

One geneticist reported that: “What GWASs do is plant a flag in the landscape and say “There’s something interesting here”. Next comes “the follow-up work to determine what that interesting thing is”.

The creators of DecodeME reported that they expected to find “dozens or hundreds of DNA differences that tilt the balance one way or another, changing someone’s risk of having ME/CFS.”

Once the DecodeME researchers find those genes, they’ll try to determine common pathways that have been disrupted in ME/CFS. DecodeME reported that they chose to study 20,000 people because other studies of this size generally found around five causal links between DNA and a disease.

The studies 20,000 person size was chosen because other studies of that size have commonly uncovered 5 causal links to disease.

The study’s 20,000 person size was chosen because other studies of that size have commonly uncovered 5 causal links to disease.

Our understanding of the role genetics plays in the development of ME/CFS at this point is pretty paltry – another reason for this study. A Utah family/genealogical study found “a strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome.” Several twin studies have suggested a genetic link to fatigue and/or ME/CFS exists as well.

Nothing even remotely like this has been attempted before in this disease. Given the rather meager stabs in the dark from the past genetic studies in ME/CFS,  there’s no telling what this big exploratory study will find. A cluster of SNPs whacking the HPA axis or perhaps the energy metabolism, or the cardiovascular system or perhaps like the macular degeneration study, something totally unexpected.

Two mysterious SNPs found in Crohn’s disease  provide an example of how potentially fulfilling the GWAS results can be. The two gene variants researcher found impaired the removal of damaged cellular components (autophagy). The plethora of damaged cellular goods, in turn, impaired the clearance of intracellular bacteria – and it was those intracellular bacteria which were causing the chronic inflammatory state in Crohn’s.

Prior to the GWAS study, no one dreamed autophagy might be a possible problem in Crohn’s.

Foundational Genetic Study – Every Disease Needs One

Getting at the potential genetic risk factors for a disease is the kind of foundational study that every disease needs.

DecodeME is looking for 20,000 people to participate.

DecodeME is scheduled to begin work in September and begin recruiting early next year. Its huge size means DecodeME may be bumping up against something Suzanne Vernon at the Bateman Horne Center warned against – the need to recruit enough real ME/CFS patients to fill the big studies that are going to start showing up in this disease.

The ME/CFS megastudy –  presents a test for DecodeME – and the ME/CFS community – as DecodeME attempts to fill an ME/CFS study that’s magnitudes larger than any that have been attempted before.

The study will use a variety of methods to get across the goal line including PR campaign in early 2021 that includes press releases and TV and radio interviews; a patient-led social media campaign on Facebook, Instagram, and Twitter; digital advertising; and engagement with advocacy groups, and, of course, word of mouth.

Sonya Chowdhury gets the challenges that lie ahead:

“Simply put, we cannot do this without the determination and support of people with ME/CFS. Recruiting the 20,000 people we need is challenging – but absolutely achievable, by working in partnership with the CureME Biobank, charities, patient advocates, local support groups and others. People with ME/CFS can register their interest right now on the DecodeME website.”

So far, DecodeME is off to a good start with over 3,000 people registering as of yesterday.

Anyone with ME/CFS aged 16 years or over from the U.K. who wants to take part in the DecodeME study, or find out more, can register their interest now at Actual study recruitment will start next year, but let’s get the pool of possible participants filled to the brim to get this study off to a good start. DecodeME reported that

“Participants will be diagnosed using the CureME questionnaire that has been in use for the UK ME/CFS Biobank for several years. This is addition to participants reporting that they have been diagnosed with ME or CFS by a clinician. Participants simply need to answer a questionnaire and provide a saliva sample to be in the study.”

Update – Several media articles have popped up on the study including two from The Times and this superb “long read” on ME/CFS.


Help keep Health Rising on the Web! Support us during our quickie Summer Fundraising Drive. Click here for more.

Health Rising's Quickie Summer Donation Drive is On!

Community support allows Health Rising to keep the ME/CFS, Long COVID and fibromyalgia communities up to date with the latest research and treatment news. If you find that helpful please support us.

Thanks for your support :)

Pin It on Pinterest

Share This