Preprint Identification of Novel Reproducible Combinatorial Genetic Risk Factors for [ME] in [DecodeME Cohort] and Commonalities with [LC], 2025, Sardell+

[ME/CFS Science Blog]

I suppose their combinatorial analysis can be useful to get new or clearer findings, but in this case, it seems to have made things more complicated and muddled.

Their disease signatures map to 2,311 genes, while humans only have approximately 20.000-25.000 protein-coding genes.

 

[mariovitali]

I am still working in trying to connect the list of genes from this paper with previous research efforts. Some new findings :


NLGN1 : Appears on the Snyder study (HEAL2)

CYP7B1 : The node of this gene appears on the network analysis (2017) - towards the center bottom :




CH25H : Also identified by previous work (read also what I mention related to Ubiquitination (Snyder et.al) , see below :



Source : https://www.healthrising.org/blog/2023/10/21/ai-driven-chronic-fatigue-syndrome-clues/

UGGT1 : A gene directly linked to N-Linked glycosylation. I believe we will be seeing N-Linked glycosylation in the -hopefully near- future more.

I also believe that Glutamate excitotoxicity is something that needs to be looked at for sure.

 

[Simon M]

In the end they get 22,411 double-refined signatures.

Now due to quality control they could only use 10 569 of those cases

I'm not even beginning to keep up, but how is it possible to have more than twice as many double-refined signatures as cases?

 

[mariovitali]

Relevant thread on X. Note the association of CH25H, CYP7B1 (2 of core genes identified) with Epstein-Barr virus

https://threadreaderapp.com/thread/1997005812838076483.html

 

[mariovitali]

So I used the DAVID tool to enter the core genes identified by the study and I am providing the results of a Pathway analysis :
First KEGG Pathway Analysis. of particular interest the Glutamatergic synapse entry, GABAergic synapse cc @ME/CFS Science Blog



Next Reactome :

Of interest : NR1H3 (=LXRa) tagging @MelbME. Transmission across chemical synapses , NR1H2 is LXRb Receptor , Netrin mediated repulsion signals and O-Linked glycosylation.





Finally here is a functional annotation set from DAVID :


(Cell?) membrane appears to the top, note the Polar residues (=I believe directly related to Aminoacids) and my personal "favorite" which was also identified in the paper by Xiao et.al related to L-Asparagine (a key part of N-Linked glycosylation) and the potential role of glycoproteins in general.



EDIT : Removed entries related to FXR which are not part of the shown results