Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain, Md Shafiqur Rahman, et al, 2020

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voner

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Abstract
Background and Objectives Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP.

Methods Northern Europeans from UK Biobank comprising 6,914 cases reporting pain all over the body lasting more than 3 months and 242,929 controls were studied. Replication of three lead genome-wide significant single nucleotide polymorphisms (SNPs) was attempted in 6 independent European cohorts (N=43,080; cases=14,177). Genetic correlations with risk factors, tissue specificity, and colocalization were examined.

Results Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes RNF123, ATP2C1, and COMT. The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227), and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth, and years of schooling were identified. Tissue specificity and colocalization analysis highlight the relevance of skeletal muscle in CWP.

Conclusions We report a novel association of RNF123 locus with CWP and suggest a role of ATP2C1, consistent with a role of calcium regulation in CWP. The association to COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

https://www.medrxiv.org/content/10.1101/2020.11.30.20241000v2.full
 
I think this is the study from Frances Williams that has been working its way towards publication since late 2019 at least. It is an important pointer to what might turn out in ME/CFS on GWAS.

As far as I can see the methodology is similar to that already tried for ME/CFS using diagnosis or self-report in people already known to the uk Biobank in Leeds. The numbers look bigger (6,900 vs 2,000), but the inclusion criteria look a bit cobbled. Self-report of pain all over is pretty vague. Pain in hip, shoulder and knee is likely to be due to arthritis rather than muscle pain. A doctors diagnosis of fibromyalgia can mean anything, including just someone with too many symptoms.

Nonetheless, they seem to have found something and it may have a significant impact on the issue of taking ME and FM seriously. CBT and exercise are not going to change your genes!

What I have not been able to get at from the data is how many people had a gene linkage to the RNF123 gene. It might have been 5% in CWP and 15% in controls or 80% in CWP an d 40% in controls. I would like to have some idea what proportion of cases the link might be relevant to.
 
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Jonathan Edwards said:
I think this is the study from Frances Williams that has been working its way towards publication since late 2019 at least. It is an important pointer to what might turn out in ME/CFS on GWAS.

As far as I can see the methodology is similar to that already tried for ME/CFS using diagnosis or self-report in people already known to the uk Biobank in Leeds. The numbers look bigger (6,900 vs 2,000), but the inclusion criteria look a bit cobbled. Self-report of pain all over is pretty vague. Pain in hip, shoulder and knee is likely to be due to arthritis rather than muscle pain. A doctors diagnosis of fibromyalgia can mean anything, including just someone with too many symptoms.

Nonetheless, they seem to have found something and it may have a significant impact on the issue of taking ME and FM seriously. CBT and exercise are not going to change your genes!

What I have not been able to get at from the data is how many people had a gene linkage to the RNF123 gene. It might have been 5% in CWP and 15% in controls or 80% in CWP an d 40% in controls. I would like to have some idea what proportion of cases the link might be relevant to.
Click to expand...

"Conclusions We report a novel association of RNF123 locus with CWP and suggest a role of ATP2C1, consistent with a role of calcium regulation in CWP. The association to COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis."

Here's a paper I found on the internet re calcium regulation:
https://www.nature.com/articles/s41380-019-0622-y

So presumably two entirely unrelated things found at random.
 
I 'like' the association of calcium regulation with pain.

I noticed a long time ago that a type of calcium channel blocker that I was on seriously reduced my 'background' pain levels. This was even mentioned at a work capability assessment. In his report the doctor took the piss and basically phrased it in such a way as to imply he thought I was delusional.

I am no longer on these, as apparently several years ago they were deemed unsuitable for diabetics.

So now I use co codamol, which is not as effective (might be, I just won't take them 24/7 but only when things get bad, or I need to sleep)

So an association between calcium and pain 'interests' me.
 
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