Preprint The Genetics of Fibromyalgia and its Relationships to Psychiatric and Medical Traits 2025 Bright et al

[Andy]

Abstract​

Fibromyalgia is a chronic heritable syndrome, with little prior genetic work taking a syndromic approach. In this study we aimed to discover genetic mechanisms underlying fibromyalgia. We conducted genome-wide association studies (GWAS) of fibromyalgia in subjects of European (EUR), African (AFR) and Latin American (AMR) ancestries, combining data from several samples (total N, 85,139 cases; 1,642,433 controls). We also conducted a multi-trait analysis of GWAS (MTAG), leveraging pain summary statistics to achieve enhanced power for fibromyalgia analyses. We then applied a series of post-GWAS methods to analyze the genetic association between fibromyalgia and a variety of psychological and physiological phenotypes.

We found 10 genome-wide significant (GWS) loci associated with fibromyalgia in EUR, 1 in AFR, 12 cross-ancestry, and 45 in the EUR MTAG. Most of these loci were previously associated with pain, cognitive function, autoimmune response, or general health measures like BMI and blood pressure. Genetic correlation analysis revealed a moderate negative correlation with physical activity, and strong genetic correlations with chronic pain, PTSD and depression (rg ≥ 0.69). Genomic structural equation modeling helped to place fibromyalgia in the context of a set of psychiatric, medical, and lifestyle traits. Additional findings regarding local genetic correlations and genetic causality point to genetic mechanisms that provide a strong basis for some of the main characteristics of fibromyalgia and its comorbidities. These findings provide potential targets for future studies to improve diagnosis and treatment of fibromyalgia.

Link

 

[shak8]

Didn't read it deeply yet.

These stood out as confounders to me. Linking FM and inactivity (and obesity and anxiety, depression) are of questionable relevance. That is because FM causes these, and does not necessarily precede onset of the FM condition. I don't see controls for this, as the authors did confirm my point.

That one database of military veterans was used---there is usually funding for research in USA veterans and this health database is only large database ( Kaiser Permanente, a health insurer, is smaller, I think) in the USA.

Using veterans' genomic data seems to me a sort of convenience sample (with high rates of diagnosis of mental health disorders due to combat--environmental toxins, high stress loads). I'll recheck to see how that genetic analysis was discerned.

So, my concern is: what was the researchers intent (was it primarily psychiatric?) and how did that influence, if it did, the data they gathered.

 

[perchance dreamer]

Fibromyalgia can also start after a physical trauma. I think calling fibro heritable is too broad a generalization.

 

[rvallee]

the strongest of these associations were with pain phenotypes (e.g. chronic pain, joint pain), traits directly related to pain (e.g. osteoarthrosis, spondylosis, migraine), autoimmune disease (erythematosus lupus) and psychiatric disorders (e.g. depression)

Given that the psychiatric disorders data set itself contains false data from people with all sorts of other illnesses, something that has been known for years and is easy to find out, this makes for a very different story than they are describing. They seem to have tried very hard to make fibromyalgia appear psychiatric, found the opposite, and still insist on it by pushing the weakest association they found, one that even if true makes far more sense as a consequence of.

It's hard to imagine any progress can be made when bias is so heavy and constant. It corrupts everything at every single step. Not much difference from Wessely trying to pin "chronic fatigue" on depression, which he claims having disproven is one of his important findings, knowing very well that the vast majority of MDs believe it, and would never correct anyone about it, and likely said it himself many times when it was convenient to him.

Hopefully the genetic data may still be useful, but the interpretation isn't. Someone who actually reads through may get something out of it, though:

In a gSEM analysis, fibromyalgia co-loaded with chronic pain and migraine, as well as with endometriosis, autoimmune response, insomnia, and physical activity, but not with psychiatric traits. This suggests that fibromyalgia may be contextualized more as a pain and autoimmune trait than a psychiatric trait, even though the genetic correlations with psychiatric traits such as PTSD and depression are quite high.

And those correlations are easy to explain, we know those patients are coded this way for no legitimate reason, and where there is a legitimate reason it's entirely a consequence of.

Here is a great evidence of how bias is making it impossible to make progress:

A moderate negative genetic correlation between fibromyalgia and physical activity (rg = −0.5 ± 0.03) reinforces the importance of physical activity as a possible treatment for fibromyalgia symptoms [2] (alternatively, that fibromyalgia itself causes reduction in physical activity, as seen in the bidirectional results in the MR analysis).

Not only is the alternative explanation they put in parentheses far more plausible, more rational, it is literally known and easy to find out, but it's put there as some off-hand idea because it doesn't conform with the traditional mythology. Obviously none of this reinforces the importance of this junk, what the hell?

In total, our results provide novel insights into the genetic architecture of fibromyalgia, providing novel information about its genetic association with pain, autoimmune response, psychiatric traits, and lifestyle.

Here the role of lifestyle is entirely physical activity, which is a known consequence of, but they present it, as is tradition, as the solution. Being unable to exercise because of poor health is not in any way a lifestyle issue, good grief a child can easily understand this, even if their academic performance is "repeated the 3rd grade twice". Holy hell this profession is so damn chaotic in how it can be good and bad at the same time.