Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

[forestglip]

For members that are interested in exploring the data from DecodeME, such as to see if certain genes are near significant loci, here is a link to the summary stats on LocusZoom: https://my.locuszoom.org/gwas/894183/

I wasn't sure if I could share it publicly, but Chris Ponting kindly pointed out that the summary stats are released under a CC-By Attribution 4.0 International license, so sharing is allowed.

As an example of how to use LocusZoom to look at a gene:

1. Find the location of a gene of interest. One way is to go the GeneCards page for a gene, scroll down to the section that says "Genomic Locations for ... Latest assembly", and copy the location which looks like this: 'chr6:31,575,565-31,578,336'
2. Click the link that says "region page" on the LocusZoom page above. Paste the gene location you copied into the search box and press Enter, and it'll take you to the gene.
3. You can zoom in or out by pressing Shift while 'scrolling' (e.g. drag two fingers on laptop touch pad or spin wheel on mouse).

Spoiler: Steps I used for uploading

Download gwas_1.regenie.gz and gwas_qced.var.gz from OSF, run this code in a terminal in the same folder as the files to make a file suitable for LocusZoom, then upload to LocusZoom and set options as indicated in screenshots.

# Filters to only QCed variants, removes non-needed columns, then sorts. Deletes intermediate files at the end.
summary_stats_file='./gwas_1.regenie.gz'
qced_var_file='./gwas_qced.var.gz'

awk 'FNR==NR {if (FNR>1) ids[$1]++; next} FNR==1 || ($3 in ids)' <(zcat "$qced_var_file") <(zcat "$summary_stats_file") > gwas_1_filtered.txt

awk 'BEGIN { OFS = "\t" } {print $1, $2, $4, $5, $6, $13, $14, $16}' gwas_1_filtered.txt > gwas_1_minimal.txt

awk 'NR==1; NR>1 {print $0 | "sort -k1,1n -k2,2n"}' gwas_1_minimal.txt | gzip > gwas_1_sorted.txt.gz

rm gwas_1_filtered.txt gwas_1_minimal.txt

The script makes a file called gwas_1_sorted.txt.gz, which you would upload to LocusZoom. These are the options I set while uploading:

 

[forestglip]

I posted in another thread, but I think this is notable enough to mention here. In a large GWAS (122,341 European ancestry cases and 729,881 controls) of anxiety-related traits (GAD, panic disorder, social phobia, agoraphobia or specific phobias), MAGMA tissue enrichment was tested.

The four most significant tissues are the same as in DecodeME, and in the same order: Frontal Cortex, Cortex, Anterior Cingulate Cortex BA24, Nucleus Accumbens.

Maybe this indicates that similar brain structures are affected in both types of disorder.

Supplementary Figure 89: MAGMA tissue expression analysis to test tissue enrichment of 53 specific tissue types for ANX genes (derived
from the main ANX GWAS meta-analsis (Ncases = 122,341, Ncontrols = 729,881)).

From DecodeMe:

 

[Kitty]

The four most significant tissues are the same as in DecodeME, and in the same order: Frontal Cortex, Cortex, Anterior Cingulate Cortex BA24, Nucleus Accumbens.

Maybe this indicates that similar brain structures are affected in both types of disorder.

I wonder if we could ask the question the other way round: what traits or disorders are associated with these brain regions, in this order of ranking?

(Possibly not, just thinking aloud.)

 

[forestglip]

I wonder if we could ask the question the other way round: what traits or disorders are associated with these brain regions, in this order of ranking?

I think it's likely that it's not actually all these brain regions affected in these disorders. Similar genes are expressed in different parts of the brain, so if only one brain region is actually causal (say, frontal cortex) and thus is significant in MAGMA, then I think it's possible that other brain regions will be significant too just from having similar patterns of gene expression to the frontal cortex.

But the main thing of interest, I think, is that the pattern of GWAS genes in the two disorders is so similar that the same top four tissues were significant in both. Though, which, if any (maybe all), of these four tissues are actually relevant, is probably still an open question.

We could look for similar patterns in MAGMA analyses in other disorders, which I did yesterday, and none but anxiety, of the MAGMA plots I previously compiled, look to be quite so similar.

[Edit: Realizing now that the last part is probably all you were asking anyway.]