Geoff’s Narration
The GIST
Just months after the publication of the first large ME/CFS GWAS study comes an enormous FM GWAS study. Notice how these two diseases seem to be marching hand in hand. Both are greatly underfunded, both are still struggling for recognition in some circles, symptoms define both, and both are now getting validation from large genetic studies.
“These findings establish a firm biological basis for a condition long defined solely by its clinical symptoms, and whose validity remains debated in some circles.” FM GWAS
“DecodeME’s results, grounded in the principles of statistical genetics, now place ME/CFS research on a firm biological foundation.” DecodeME GWAS
At Risk Genes for Fibromyalgia
Like the DecodeME ME/CFS study, this FM GWAS study aimed to uncover the “genetic architecture” of FM; i.e. the genes that increase the risk for it.
Size matters in genome studies. The recent FM preprint, “The genetic architecture of fibromyalgia across 2.5 million individuals“, was about 8 times larger than the DecodeME study and found three times as many “genetic risk loci” (24 to 8). (When Decode joins with Ian Lipkin’s genetic work in the US, more genetic loci for ME/CFS should pop up. Because the FM study relied on electronic health records, the FM group may not be as well-defined as the ME/CFS group.)
Health Rising’s Quickie Summer Donation Drive is On!Genetic risk loci refer to regions of the genome with significant genetic variants that are associated with the disease. They could be said to represent the “genetic architecture” of the disease. They are the areas of the genome that appear to have put you or me at risk for FM.
The most significant variant was an odd one: a variant (rs149109767-A) which results in a glutamic acid deletion in the causal gene for Huntington’s disease (!). That variant alone increased a person’s risk of coming down with FM by 9%. (The variant in FM is much smaller (loss of one amino acid) than the alterations found in HD and does not take place in the same part of the gene.)
Other gene variants affect things like interneuron excitability (causing subclinical seizures), hippocampal functioning (causing memory impairment), the kynurenine pathway, dopamine (motivation and cognition), sleep, natural killer cell functioning (!), neuroplasticity, excitatory neurotransmission, testosterone metabolism, cognitive issues, microglial activation and neuroinflammation, lipid and mitochondrial issues.
The study, in other words, confirmed that people with FM have a genetic predisposition to many of the biological abnormalities studies have found.
THE GIST
- The first big GWAS FM study scored by finding many significant regions of the genes we are born with that appear to contribute to FM. That finding, as the authors said, puts FM on a “firm biological foundation”.
- The genes highlighted in the study affect things like interneuron excitability (pain processing/subclinical seizures), hippocampal functioning (memory impairment), the kynurenine pathway (pain and others), dopamine (motivation and cognition), sleep, natural killer cell functioning (!), neuroplasticity, excitatory neurotransmission, testosterone metabolism, cognitive issues, microglial activation, neuroinflammation, lipid and mitochondrial issues.
- The study, in other words, confirmed that people with FM have a genetic predisposition to many of the biological abnormalities studies have found.
- Like ME/CFS, the genes almost wholly pointed to the brain, and, in particular, in FM, to genes that affect pain and sensory processing. Genetic variants that affect similar areas of the brain were found in both ME/CFS and FM.
- Many genes found in FM have also been found to contribute to other illnesses. This suggested to the authors that the genetic architecture found in FM constitutes a kind of “transdiagnostic” genetic vulnerability that reaches far beyond FM itself. That “vulnerability profile”, they believe, affects core neurobiological systems such as central nervous system excitability, dopaminergic/serotonergic signaling, and neuroimmune stress.
- It’s also found in diseases like ME/CFS, chronic pain conditions, IBS, PTSD, depression, and more. A ChatGPT 5.0 analysis concluded that “DecodeME’s strongest loci for ME/CFS sit exactly where you’d expect such a vulnerability to live“.
- Two genes, in particular, offer new treatment pathways for FM. Drugs for them are not available right now, but are under development and being tested.
- Coming up – PrecisionLife takes genetic analysis to the next level in ME/CFS.
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Another Brain Disease…
The DecodeME study suggested that the genes found in ME/CFS mostly affected the central nervous system; i.e. its genetic roots suggest that the failure point begins in the brain.
Fibromyalgia, of course, has always been thought of as a central nervous system disease. In fact, it’s been called the prototypical central sensitization disorder, so it was no surprise when the researchers determined where in the body the gene regions associated with FM were most active that the brain popped up in spades.
Like ME/CFS, the genetic underpinnings of FM point to the brain.
All the tissues with significant enrichments (high expression of the genes found) were found in five regions of the brain, found in the cerebral cortex and basal ganglia that process pain, movement, motivation, and emotion. They included the cortex (general cortical gray matter), the frontal cortex (BA9), and the caudate nucleus (part of the striatum). The putamen (also striatal) integrates motor and motivational information, and the anterior cingulate cortex (ACC) is a key hub for the emotional and attentional dimensions of pain.
Plus, 12 of 13 enriched cell types were neurons. The strongest association was with neurons from the dentate gyrus, which is a part of the hippocampal region that contextualizes or helps us to understand sensory experiences, including pain.
Other high areas of activity were also found, interestingly enough, in neurons in the “second brain” – the gut and neurons largely involved in pain and sensory processing (diverse interneurons, cortical projection neurons, and striatal neurons). The only non-neuronal cell type to make the cut – 0pulmonary neuroendocrine cells – was, guess what, a specialized sensory cell which has neuron-like properties.
No other cell types were affected! Given the emphasis on neurons involved in sensory and pain processing, it’s no wonder that FM has been called the prototypical central sensitization syndrome. It’s the only chronic pain disease that’s not focused on a tissue – it appears to simply consist of a kind of widespread nervous system derangement, and, if this study is correct, people with FM were set up from birth to experience it. One of the encouraging things about these findings is how well they fit with what we know.
Multiple Disease Overlaps
The gene variants highlighted in FM also play a role in many other diseases.
As expected, the most extensive and significant genetic overlaps were with musculoskeletal and pain disorders – particularly those associated with widespread pain.
We know that people with any pain disorder, such as joint pain or low back pain, are at increased risk for FM, so it made sense that genes highlighted in FM also placed people at risk for migraine, joint and low back pain, and, interestingly, hypermobility syndrome.
Given its strong nervous system roots, it was perhaps not surprising to see “substantial genetic correlations” with diseases like post-traumatic stress disorder (PTSD) and depression (and more modest associations) with anxiety and insomnia.
Significant genetic overlaps were also found with irritable bowel syndrome, functional dyspepsia, asthma, rheumatoid arthritis, and polycystic ovarian syndrome. (Interestingly, FM was more genetically correlated with the seronegative form of RA.) Genetic correlations with autoimmune disorders were present but modest.
ME/CFS – Siblings, Kissing Cousins, or Distant Relatives?
With regard to ME/CFS, a strong correlation with the core clinical symptom of malaise and fatigue was found. The fact that 2 of the 8 genetic loci that popped up in the ME/CFS DecodeME study (LFM4 (chr13q14.3) RABGAP1L region (chr1q25.1) also showed up in the larger FM study indicates some significant overlap is present. The CA10 gene found in ME/CFS in the DecodeME study provides another potential association as it’s been linked to chronic pain conditions that affect multiple areas of the body.
The DecodeME analysis also suggested that ME/CFS was primarily a central nervous system disease. Indeed, the 13 tissues that met statistical significance were all found in the brain. As in the FM study, immune and muscle tissues did not make the cut.
The brain regions impacted by the genetic variants found in the two diseases were similar. Of the five brain regions highlighted by the FM study (cortex, caudate, frontal cortex, putamen, and anterior cingulate cortex), three showed up in DecodeME (frontal cortex, putamen, and anterior cingulate), plus both diseases featured parts of the brain associated with the basal ganglia (striatum, putamen, and caudate).
Call the two at least kissing cousins.
Core Vulnerabilities Affecting Multiple Diseases Identified?
The genetic overlaps found in so many diseases caused the authors to refer to the “profound pleiotropy” found in the gene variants associated with FM. Pleiotropy concerns the ability of a gene variant to cause many different effects and symptoms. In this case, the genes implicated in FM have been associated with negative effects in a surprisingly wide variety of diseases.
The authors believe the genes found in fibromyalgia may represent a core group of genes that play a role in many other genes.
This resulted in the authors proposing that the genetic implications of the study may go well beyond FM. They believe that the “vulnerability profile” in FM affects core neurobiological systems such as central nervous system excitability, dopaminergic/serotonergic signaling, and neuroimmune stress that play a role in other diseases. Because these systems are embedded in the nervous system, they can produce symptoms across the body.
The authors suggested the genetic profile found in FM may “capture a core, transdiagnostic vulnerability” which results in pain amplification, stress sensitivity, etc. in a range of diseases (FM, ME/CFS, chronic pain conditions, IBS, PTSD, depression, and more).
A ChatGPT 5.0 analysis of this proposal concluded that “DecodeME’s strongest loci for ME/CFS sit exactly where you’d expect such a vulnerability to live“. ChatGPT believed this association will likely increase as bigger GWAS ME/CFS studies are published.
Because these diseases feature a “core, transdiagnostic vulnerability”, future studies and clinical trials should include all these diseases, and indeed, that’s what advocates are trying to accomplish and what David Putrino is actually doing at Mt. Sinai.
New Treatment Targets
“These loci represent the first genetically-supported molecular targets for fibromyalgia” the authors
HTT/GPR52
The fact that the HTT gene and its regulator GPR52 were both highlighted suggested that drugs targeting the GPR52 gene in Huntington’s Disease (HD) are a possibility. This surprise entrant – a gene best known for its effects in HD – may be a risk factor for FM because it’s expressed in areas of the brain that process pain signals.
Several GPR52-enhancing and inhibiting drugs are under development.
CELF4
“The CELF4 locus fibromyalgia risk locus provides a direct genetic rationale for exploring CELF4-based gene therapies…for fibromyalgia”
Two genes in particular stood out; one plays a key role in pain processing.
GPR52 was a bit tangential. This was not the case for the CELF4 gene, which seems to hit all the right spots. The protein produced by this gene occurs right smack in the neurons found in parts of the brain that are of high interest in FM and ME/CFS. They include the dorsal horn (pain signaling), brainstem (autonomic nervous system, sensory processing), amygdala (fight or flight), and cortex (cognition, executive functioning – frontal cortex).
Removing CELF4 from mice sets them up for a nice case of FM by increasing nervous system excitability, pain sensitivity, and altering the release of two neuropeptides (substance P and CGRP) known to play a role in FM. (It also heightens the mice’s susceptibility to seizure.) A CELF4 gene variant that results in reduced CELF4 levels, then, could play a core role in producing FM.
Several animal studies that seek to boost CELF4 levels are underway. The authors noted that the strong CELF4 signal found in FM suggests that pharmaceutical companies should begin to explore CELF4-enhancing drugs in FM.
Conclusions
The first big GWAS FM study scored by finding many significant areas of the genome that appear to contribute to FM, thereby, as the authors said, putting FM on a “firm biological foundation”. Like ME/CFS, the findings almost wholly pointed to the brain, and, in particular, to genes that affect pain and sensory processing.
The many genes found in FM, which also contribute to other illnesses, suggested to the authors that genetic architecture found in FM constitutes a kind of “transdiagnostic” genetic vulnerability that reaches far beyond FM. That “vulnerability profile”, they believe, affects core neurobiological systems such as central nervous system excitability, dopaminergic/serotonergic signaling, and neuroimmune stress and is also found in diseaeses like ME/CFS, chronic pain conditions, IBS, PTSD, depression, and more.
Indeed, a ChatGPT 5.0 analysis concluded that “DecodeME’s strongest loci for ME/CFS sit exactly where you’d expect such a vulnerability to live“.
Two genes, in particular, offer new treatment pathways for FM. Drugs are not available right now but are being tested.
- Coming up – a talk with the CEO of Precision Life as it takes the genetic analyses in ME/CFS to the next level
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It’s so nice to read about scientific research being made on fibro! They are so few and far between, this will fuel my hope machine for a while. And with possible treatment pathways, amazing!
I was a healthy competitive athlete and getting ready to compete when I thought I had the flu after training one day . After 2 months of testing multiple times specialists and no one ever mentioned the word Fibromyalgia and I had never heard of it . I was diagnosed with a severe case of depression.I was put in a mental health hospital and given multiple rounds of ECT which made me worse . IThe next 10 years Iwas put on every imaginable antidepressant every combination and years of of high opiates including phentanyl. I could have died as they put me on too high a dose .and eventually developed severe IBSC .. Four hours of excruciating pain in the bathroom every morning for 3 years. I had to pad my bathroom in case I lost consciousness I was put on every combination and imaginable combination of GI meds. LDN has helped my fibro pain .. I also suffer from PTSD from childhood sexual abuse. Thank you for the work you are doing . I will include it in why I have to try to get thru my day . Every day is such a struggle and every other commercial I hear on TV is to fix male sexual dysfunction . I always think thru the tears I cry every day . What about us ?Thank you for your work. I am 75 suffering from severe depression , gi issues major back problems . I tell myself it could always be worse and now it looks like I need back surgery and oh I forgot ZI had breast cancer last year. Maybe it’s too late for me but I pray you will eventually be able to help this horrible suffering some day for others.Thank you !
What a rough time you’ve had Robyn. I’m so sorry you’ve had to go through so much. I wish federal officials in charge of funding had to be made to read your story and so many others.
You are certainly not alone. You can find many other stories and add your own if you wish to our Lives Interrupted project.
https://www.healthrising.org/bm-li-view-stories/
Check out Fina’s comment below – she’s gone through much the same thing.
Oi Robyn Green, já o meu problema é o inverso ao seu a 14 anos fiz cirurgia de coluna lombar, sofro de cansaço crônico, e atualmente minha ida ao banheiro ficou frequente. Tem dias que evito comer. Dores constantes, e oro para que no futuro espero que seja próximo as pesquisas avance, tenho 54 anos as minhas limitações são muitas, espero que minha passagem pela terra seja breve.
I will pray for you Robyn🙏.
My story is similar but when I was having histamine explosions inside my body and already had been seeing many many doctors that had not one bit of science behind there conclusions, they sent me to a shrink that had his student evaluate me.
Because I had already been past frustration with the system, they decided to tell me I had a mood disorder….I said to my wife “let’s get up and leave”.
I knew that my immune system was jammed up because I had already cut way back on my diet and felt my guts heal…I actually went into complete remmision simply by changing my diet!!
Wow! I am so glad to hear of solid evidence that explains the symptoms that people with FM have to live with.
I wonder if I can get tested for these gene variants.
I also wonder what life will be like if medications are found that can treat FM.
I have had FM for 39 years and the guarded hope that I can have a better future where I will be able to function better!
Many with fibromyalgia clearly benefit from low-dose nicotine patches. But there doesn’t appear to be any research connecting nicotine directly to these two genes. Only indirect, but logical possible interactions.
An AI response on nicotine and GPR52
GPR52 and nicotine
Nicotine affects other receptors: Nicotine has been shown to upregulate the expression of other G-protein coupled receptors, such as GPR51. This suggests nicotine could have a broad impact on the G-protein coupled receptor system.
GPR52 and dopaminergic pathways: GPR52 is found in the striatum, a brain region heavily involved in the dopaminergic system, which is a primary target of nicotine. Nicotine affects dopamine levels and the associated pathways, indicating that GPR52 may play a role in how the brain responds to nicotine.
Potential therapeutic target: Because of this functional crosstalk, the discovery of GPR52 agonists (substances that activate GPR52) is being explored for treating conditions related to addiction and dopamine pathway dysfunction, such as nicotine dependence.
Short summary:
*GPR52 activation seems to increase cAMP (cyclic AMP). cAMP is quite an important messenger molecule.
*Chronic nicotine use has the potential to impair the cAMP response binding protein. It thus has the potential to prevent cAMP produced by GPR52 to work on its target genes and interrupt the signalling cascade.
* GPR52 seems to balance dopamine signalling. Dopamine signalling plays important roles in chronic pain. Combined it means nicotine has potential to adjust dopamine signalling and with it pain response.
Sources:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8428802/
“The G protein-coupled receptor 52 (GPR52) is an orphan receptor that is selectively expressed in the striatum and regulates various brain functions through activation of cAMP-dependent pathways.”
https://pubmed.ncbi.nlm.nih.gov/21740234/
“Chronic nicotine administration impairs activation of cyclic AMP-response element binding protein”
Also from https://pmc.ncbi.nlm.nih.gov/articles/PMC8428802/:
“Moreover, GPR52 is colocalized exclusively with dopamine D2 receptors in medium spiny neurons (MSNs) in the striatum and has lesser expression in neurons of the medial prefrontal cortex.”
and “Thus, GPR52 signaling via cAMP could oppose activity of D2 signaling in the striatum while stimulating the D1/N-methyl-d-aspartate (NMDA) function in the frontal cortex.”
=> Combined this IMO means: GPR52 is sitting only on cells in the brain that also have D2 (subtype of dopamine) receptors.
=> GPR52 is thought to be able to modify the dopamine response of the neuron they are located on.
=> Chronic nicotine use is able to modify / intercept parts of this mechanism.
=> Chronic nicotine use thus has good potential to modify neuronal response to dopamine. There are plenty of papers on the role of dopamine on pain relief, managment and chronic pain plus on neuroinflammation.
It is a tricky mechanism with side effects though.
Is it correct that these are genes we are born with and which were dormant while we were healthy and then somehow got activated in which caused our illness? If so is it possible to make them go dormant again?
I think this sounds right Nancy – “epigenetics” – there are plenty of people who have got over really bad CFS in time
Dear Nancy, I saw your comment and, being a professor with large knowledge of genetics as well as physiology and fibromyalgia (we are developing a test to objectively quantify chronic fatigue/PEM; looking for funding/investors), would like to respond to it. I have academically worked on genetic as well as acquired diseases and can tell you the following: while a genetic profile (as determined here) may make us susceptible to develop a disease like FM, the fact that FM is not there at birth tells us that the found gene variants DO NOT have a large impact on the development of FM. The gun may be loaded, but the genes are not pulling the trigger. When diseases develop later in life (i.e. later than e.g. 2 years old) as mostly with FM, the impact of the environment is of much greater importance. These are often adverse child effects, (large) negative experiences during one’s youth (in science they call this nurture instead of nature). While it is still unknown what the effect of the identified gene variants is on our physiology and it is still impossible to manipulate those putative effects locally, treatment developments should best be focused on the latter (environmental cause). I hope this clarifies your question.
healthiest regards, peter
Thank you Peter!
Dear Peter, thank you for your explanation regarding the gun / genes / trigger which is helpful and encouraging as a mother !
I was diagnosed with FM over 17 years ago ,it was fantastic to have a diagnosis and be believed ! That the symptoms I was experiencing was not just in my head.Early experience of poverty no hot water/ heating / bathroom / no indoor toilet even in the late 50’s early 60’s , sexual abuse by paternal grandfather and subsequent early life experiences growing up in a household with a schizophrenic father may well have had an impact on developing FM laterc.(My heart goes out to you Robyn)I too hope research will provide treatment or a cure to manage this miserable condition.Me and my 4 siblings did well eventually because of a dear and exceptional nurturing mother !
I have a genetic polymorphism (see below) and I have spent 35 plus years trying to live with Fibromyalgia, CFS/ME, being diagnosed at age 30. Unable to work I had to file for SSDI in a time when FM was not on the list of health problems for disability. After jumping through hoops for 5+ years I was able to get SSDI due to the medication that I took for these condition. Then in 2015 I had genetic testing done for MTHFR polymorphism of
the following
MTHFR A1298C = compound heterozygous mutation and
MTHFR C677T = compound heterozygous mutation
I have several siblings with other variants of this MTHFR polymorphism, as well as several nieces and nephews, we have all been tested and a couple have not. I can point at other relatives that probably have the same genetic MTHFR problems. So basically, I trying to say I’m not educated about any genetics testing or abnormalities but it just ‘feels’ to me that this genetic problem contributes to the FM problem. I would love to see, or hear from someone who could answer for me if this is possible. I can remember extreme joint pain from the age of 4, also ADD/ADHD, anxiety, and depression all my life…if anyone could enlighten me on the possible involvement or not I’d be grateful, not that it would fix it 😉 but it would be nice to hear.
Thank for reading this. I’m keeping my fingers crossed for possible answers to what causes FM and the possibility of managing it better for those of us who get totally debilitated by FM CFS/ME.
I’m not really up on MTHFR anymore but yah, it was a big thing in ME/CFS and FM for quite awhile. My understanding is that while other gene variants are clearly involved it is part of the picture.
These are just the genes we are born with… They are our genetic heritage and their expression can change over time due to epigenetics. So this blog is not on epigenetics. (The last one was). I think of them as them as displaying the weaknesses that allowed things like ME/CFS and FM to occur – probably with an assist from epigenetics; that is they constitute our inborn genetic vulnerabilities which epigenetic events could exacerbate.
Thanks for your reply.
Thanks Cort.
During the tedious process of analyzing my genes, as shown in Figure 4, (https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-07203-w), I discovered that the gene NOD2 was mentioned 14 times, a gene related to Yao Syndrome.
see: https://forums.phoenixrising.me/threads/yao-syndrome.93918/#post-2485834
Interestingly, this NOD2 is associated with nearly all known symptoms of ME/CFS.
Would you be able to post links to the studies and drug development for the mentioned genes?
‘ the failure point begins in the brain’
Yes!
So let’s stop wasting time on viruses and the immune system ( other than where it crosses over into the CNS)
Just wait for the next genetic blog, Matthias – it’s mostly about immune genes – the two must go together and I very much like your idea of immune disruptions that reach the brain.
Rather than immune disruptions that reach the brain, I think the immune disruptions are primarily IN the brain /CNS.
As the control centre, that then impacts the ANS, HPA etc.
My view is the t cell exhaustion issue is caused by a faulty ANS, which is caused by a faulty brain rife with neuroinflammation
Certainly could be. Sickness behavior, after all, comes from the brain.
Speaking of which, did you see this recent paper by Komaroff and Dantzer:
https://www.sciencedirect.com/science/article/pii/S2666379125003325
I think this theory is also pretty close to the mark:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9174654/
And this research isn’t specific to ME/CFS but I think very relevant:
https://www.science.org/doi/10.1126/sciimmunol.adm7908
I was able to heal from Mulitple Chemical Sensitivities by applying brain retraining techniques. I found that when I panicked upon exposure I was sending a threat to my body that it was in danger and my body overreacted to the exposure. Once I changed my thoughts my body stopped reacting and my symptoms subsided. Of course I still try to avoid exposure but only because the fumes are not healthy. This made me realize how much our bodies respond to what our brain tells it.
You are not at all alone. Eleanor Stein MD tried everything she could think of to recover from ME/CFS and MCS to no avail. She recovered from MCS almost immediately and while it took several years for ME/CFS she recovered.
If FM is correlated with seronegative RA, how does one confirm the RA? I test positive for RF and the numbers are increasing yearly. But if they test for the next level which would indicate positive for RA, it’s negative. I wonder though, these seronegative diseases, how does one confirm the diagnosis?
It’s more through physical assessments: swelling on both sides in hands, wrists or feet, imaging that shows inflammation in the joints, and lab work which shows inflammatory markers, by excluding everything else it could be – and then trying RA drugs to see if they work. 🙂
Hola Robin, después de un burnout en el trabajo me ocurrió lo mismo que a ti con : diagnóstico de depresión severa crónica grave, toneladas de fármacos y 11 sesiones de electroshocks borrando 40 años de mi vida.
Des de entonces FM, SFC, SQM y EHS.
Google translate: “Hello Robin, after a burnout at work, the same thing happened to me as it did to you: diagnosed with severe chronic depression, tons of medication, and 11 electroshock sessions erasing 40 years of my life.
Since then FM, CFS, MCS, and EHS.
A HUG!”
UN ABRAZO !
Thanks very much for this and all your work. Hugely appreciated. And so good to have a biological “justification” for the condition. Meanwhile my own instinctive/layman’s interpretation of all this stuff about nervous system vulnerability, PTSD, etc, is to continue with what has helped me most so far: yoga/meditation, with emphasis on meditation, stillness, ultra-slow breathing to very slow, calm meditation music on ytoob, for a good one hour a day, maybe two. The effects are v powerful. After 18 months of CFS, with first 3 months in bed not moving, I will be out doing a small 20 min run this afternoon in the woods. Never give up hope! It is fixable. Hope this may help someone, and thanks again
Turning down the alarm center of the brain. Nice!
As a FM sufferer I have always felt FM is the gateway to other illnesses/diseases. My casual observations of others comments in support groups and my own experiences have led me to believe this. Please keep working on this as it’s very debilitating for so many of us.
Always eager to highlight fibromyalgia and other nociplastic disease findings.
I just don’t know how you do it, Cort. It exhausts me just reading it. I can’t imagine wading through all of the studies to make sense of them all. Thank you.
Dear Cort, what’s GWAS short for? Thank you!
The results of this study are fantastic. What a breakthrough! MY head hurts all the time. My skull has physical pain. I always thought my brain was involved. I have had both FM and ME for 32 yrs. It hit when I was 41; in the prime of my life. I was lucky. I have a husband who has stood by my side all this time, especially in the early years when I couldn’t work and we needed the money. He worked from home and became my primary health care provider. My health has gotten better in my later years. I don’t sleep as much and I can cook dinner and do small chores. I can even drive myself places like the doc. off. or to the mall to shop for an hour– so keep the faith. Hope will help to keep a smile on your face and in your heart. I have always tried to keep a positive attitude about my life. God put me on this earth for a reason so I put one foot in front of the other and keep on truckin. Take care everyone.
I should have spelled that out. Genome wide association study – which studies more common genetic variants – as opposed to a whole genome sequencing (WGS) – which studies the entire genome.
Thanks!
Many with fibromyalgia clearly benefit from low-dose nicotine patches. But there doesn’t appear to be any research connecting nicotine directly to these two genes. Only indirect, but logical possible interactions.
An AI response on nicotine and GPR52
GPR52 and nicotine
Nicotine affects other receptors: Nicotine has been shown to upregulate the expression of other G-protein coupled receptors, such as GPR51. This suggests nicotine could have a broad impact on the G-protein coupled receptor system.
GPR52 and dopaminergic pathways: GPR52 is found in the striatum, a brain region heavily involved in the dopaminergic system, which is a primary target of nicotine. Nicotine affects dopamine levels and the associated pathways, indicating that GPR52 may play a role in how the brain responds to nicotine.
Potential therapeutic target: Because of this functional crosstalk, the discovery of GPR52 agonists (substances that activate GPR52) is being explored for treating conditions related to addiction and dopamine pathway dysfunction, such as nicotine dependence.
Hi Cort,
I just wanted to let you know that I’ve been preparing a French summary of your article about the large fibromyalgia GWAS, because I found the connections you drew with ME/CFS research particularly interesting.
I’m doing this for ME/CFS patients in France, who don’t speak English and rarely have access to this kind of scientific information.
While rereading your piece, I noticed a small typo in one of the gene names — you wrote LFM4 (13q14.3), but it should actually be OLFM4 (13q14.3), with an “O” at the beginning.
Thank you again for your insightful and detailed work 🙏
Thanks, Clemence!
Will you be at the American College of Rheumatology meeting in Chicago this week?
I’d like to meet with you.
No, afraid not. Thanks, though. 🙂
My rheumatologist diagnosed me with FM more than 20 years ago. I would like to learn more
about your research and possible new treatments for the trigger point pain I suffer.
I am now 83. My younger sister was also diagnosed with FM; her pain was significantly more
disabling than mine.
Thank you for your work.
muito obrigada por essa pesquisa <3
There are many who give supplements to help genetic pathways. Wonder is there are some DNA SNPs like glutamic gene that is affected by environmental causes. Perhaps there are some that would help detox for example as copper’s complex interactions that can increase and decrease glutamic acid.
Hi. Are you carrying out any trials for Fibromyalgia in the UK.
If so please feel free to contact me to take part.
Yours
Mr JEFFREY Bartlett
CELF4 SNP found in ME patients in this study: https://pmc.ncbi.nlm.nih.gov/articles/PMC4872418/table/tbl1/
I’m 79 years old and I suffer. I doubt I will get help before I’m gone but I do dream of just a few days without FM. There will be help eventually.
I’ve been doing the PD-5 treatment from limitless healthcenter. c om for about 5 months. it doesn’t seem like I’m getting any better, but overall I actually have. My husband says it’s has done me a lot of good in terms of balance and ability to walk and get up from chairs. I can now write without my hands shaking. I feel better now than I have felt in years, and I can feel my strength again.