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If I understand correctly, the LC GWAS had only 5,768 cases and 2,701 which is really small so no wonder they didn't find any significant hits. Here's what their Manhatten plot looks like: I haven't checked systematically but most of these do not ring a bell in relation to DecodeME. It also...

Reading some GWAS in other illnesses made me appreciate DecodeME even more. Other GWAS are usually based on (1) extracting data from big databases like the UK biobank, Finngen, AllofUS, 23andME etc. where the case definition was often poor or (2) on multiple cohorts that are combined into a...

Thanks I should probably mention that I zoom out a bit more (1Mb) than most tools like LocusZoom (around 250kb) to get an overview of the entire region around the hit. The implicated genes are probably closer to the top SNP then the region I show (so don't pay too much attention to the genes at...

Another issue is that fibromyalgia is usually not about heightened pain sensitivity when there is peripheral input. It's about constant widespread pain even without any peripheral input. So rather than just have an increased response to pain stimuli when these arise, patients seem to have the...

From the article: Looks like pacing was confused with GET.

In contrast to DecodeME, most of the participants were recruited from other cohorts which used the ICD-code M79.7 to select fibromyalgia patients. They basically combined all the major databases (All of us, UK Biobank, FinnGenn, etc.). 87% of patients were female. Most of the implicated genes...

Anyone knows more about this situation in Zwitserland? Seems a positive development, would be interesting to hear from people there what they expect from it and what it means.

Yes

A gene that hasn't been disucssed much is TAOK3 on chromosome 12 (it wasn't a Tier 1 gene). It has been previously been associated with Lupus at around the same region as in DecodeME. The vertical dotted line in the graph below shows the location for the Lupus hit (12:118244946) with the SNP...

Yes but perhaps they are in strong LD because they are related to the long RABGAP1L gene? It also looks different from the SNPs that hit the significance threshold close by and which seems more ambiguous (not sure which gene it points to). But the dragonlike-SNPs at 10^-6 probably point to...

I initially thought that the causal gene(s) for this region on chromsome 1 are too uncertain given how many protein-coding genes are packed in this region. I still think this is the case. But zooming out, it seems that there might be two independent signals close to each other. A small group...

In this German talk Scheibenbogen says agomelatin is suggested as an off-label treatment for ME/CFS to be reimbursed by insurance companies. She references the Pardini et al. 2014 trial.

I suspect these evolutionary pressures long predate the time of arrows. And because hEDS is said to be a disabling disease appearing in adolescence it would in many cases have reduced fitness. So the idea is that strong effects like the one found here would normally have been filtered away if...

I think that the effect sizes seen in DecodeME are the norm in GWAS. There's also an evolutionary theory behind this stating that if a common SNP was more strongly associated with disease, it would have been deleted. So the strong effect (OR = 1.66) found here is a bit curious and unusual...

@Jonathan Edwards how would you explain SLC39A13 showing up in this meta-analysis? Doesn't it seem to suggest a relationship between hEDS and EDS?

Yes not sure if that statement holds up, hadn't seen it. Thanks for highlighting it.

Not sure I would agree with that either: some of the genetic correlations we calculated with LDSC were quite high.

I am not sure this statement is correct by the way - regardless of the debate about hEDS in this thread. All human traits have heritability. My guess would be that if you take people with severe fatigue you might also find significant hits in a GWAS the size of DecodeME.

My own argument has been that the hEDS diagnosis likely captures a lot of people who do not have a connective tissue disorder but some other disease. Think the genetic data of this study is still consistent with that. The two hits show strong effects but it isn't very clear what they mean. They...