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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...

I think SHISA6 is the most likely candidate (FLAMES predicted it as well) but in case it's DNAH9, there might be a possible connection with (other weak candidates) DNAH10, and ERICH3 as they are all involved in cilia: the hair-like structures that stick out from the surface of certain cells and...

Chromatin openness Had a closer look at this region. The credible set has 25 SNPs and lies in the second intron of SHISA6 itself. There were three regulatory elements that included one of these SNPs of which the one to the right EH38E1847030 had the highest probability. It's mostly open in...

Yeah, the locus is not so clear or informative. Posting the analyses anyway, perhaps something clicks when in the future more info is available. Yes the colocalization analyses tries to find out if the two signals are driven by the same causal variant(s) based on these correlation patterns...

Here's a bit more about some of the candidate genes: CCDC92 CCDC92 Gene - GeneCards ZNF664 ZNF664 Gene - GeneCards DNAH10 DNAH10 Gene - GeneCards

Probably due to linkage disequilibrium, the correlation with the one causal SNP that is driving the signal. The colours indicate that the strips are SNPs that have the same correlation with the causal SNP.

Both the eqtl and phewas show that multiple studies that share the same signal. I've attached my results in Excel files. This region comes up a lot in metabolic traits such as BMI, HDL cholesterol, waist-to-hip ratio, etc. The ME/CFS risk version goes with a lower waist-to-hip ratio for a...

The credible set made using SUSIE consists of 77 SNPs in high correlation with each other. The region they span is full of regulatory elements which do not point to particular tissue or cell type. The 3D links data from ENCODE had multiple links to CCDC92 and ZNF664, so I suspect these are the...