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@James Cox Perhaps this region is of interest to you.

Hard to say because we have no dataset on gene expression that matches (the eqtl section). So Decode shows which versions of the DNA are more common in people with ME/CFS but not if a gene expression is increased or decreased.

Looks like CDYL is a gene that keeps nerve cells from becoming over-excitable. Knock-out models in mice have been linked to epilepsy and pain. CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression - PMC Cdyl Deficiency Brakes Neuronal...

The eqtl didn't found any notable results while the phewas found two other genetic studies with a similar signal: Trait PP.H4 lead_p study_ID Source Gastro-oesophageal reflux disease 0.97 1.3e-05 finn-b-K11_REFLUX OpenGWAS rfMRI amplitudes (ICA100 node 51) 0.90 5.7e-06 ubm-b-2214 OpenGWAS

Gene card: CDYL Gene - GeneCards

Another DecodeME hit that remained just below the significance threshold (p = 2.9 × 10⁻⁷). The T risk allele was present in 81.9% of cases and 79.3% in controls, resulting in an odds ratio of 1.086 per copy of T. The 95% credible set using SUSIE consists of 22 SNPs that lie in the RNA...

The benefit of this locus is that we're relatively confident that it points to DCC. The whole credible set falls inside it and other protein-coding genes are a bit far off, probably outside the Hi-C domain. In the eQTL analysis, the best match I found was also with DCC but the signal was weak...

Here's the genecard info on LRRC7. LRRC7 Gene - GeneCards

This locus was just below the significance threshold in DecodeME. The credible set includes 189 SNPs and all lie in LRRC7, which is the most likely causal gene. The eQTL showed that LRRC7 colocalized with several different tissues but with PP.H4 around 0.6-0.8, so it wasn't a perfect match...

ZNF66 is mostly known for its role in eye development. A pathogenic mutation causes severe myopia. https://www.genecards.org/card/ZNF644 BAHRL2 is a brain gene, a transcription factor that plays a role in axon extension and neuronal fate specification. It also seems to be linked to the eye and...

Perhaps not the most interesting locus but it does have a signal just below the significance threshold (p = 1.9 × 10⁻⁷) in DecodeME. The credible set lies in the gene ZNF644 which is also the most likely candidate. In the Hi-C on the 3D-folding BARHL was in the same domain and had multiple...

Had a closer look at this locus. The credible set lies mostly inside the long gene TOAK3 but also SUDS3 and PEB1. Chromatin contacts also pointed to SSRM4 as an option on the east side, but it only has contact to the most easter side of the credible interval that doesn’t hold much probability...

I also noticed that there's a very strong signal in the eQTL datasets for the OLFM4 protein. It's near the credible set but doesn't colocalize (PP.H3 = 0.973). Perhaps that was why the FLAMES algorithm made a confindent prediction for OLFM4. I personally think that PCDH8 is more likely given...

Had a closer look at this region. In finemapping, SuSiE found strong evidence for one signal but no 95% set, only an 80% set of 47 SNPs. 8 of these credible-set SNPs were in 7 regulatory elements and 4 of these elements were in the pseudogene PCDH8P1 These cCRE had the most chromatin 3D...

Looks like SOX6 helps to determine dopamine input to the striatum. Source: Disruption of SOX6 is associated with a rapid-onset dopa-responsive movement disorder, delayed development, and dysmorphic features - PubMed Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons...

Sounds like great news. I'm only wondering what the inclusion criteria will be because PAIS can be a much broader concept than ME/CFS. Perhaps that also explains the big numbers they plan to reach.

We have a lot of databases that measured DNA (the genetic code) and RNA (a measure of gene expression). So one would think that looking up the DNA variants that are associated with ME/CFS (from DecodeME) in those databases would tell us which genes it influences. For example, it could be that...

I think we already discussed this last year and argued that epigenetic silencing is more likely in both diseases. There's a thread about that study here: Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy, 2023, Seifinejad et al | Science for ME

Even though this region falls just below the significance threshold, the credible set lies entirely inside the SOX6 gene, making it quite likely that this is the relevant one. The 3D domain only includes C11orf58 as another protein coding gene. The FLAMES algorithm was also quite confident...

I'm not sure about this because these are all very small effect sizes, mutations that are common in the general, healthy population. So I see it more as small variations that aren't severe enough to cause development problems. A bit like having bigger nose or pale skin, one could also have more...