Some other relevant studies:
Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors - PubMed
A requirement for the POU transcription factor, Brn-2, in corticotropin-releasing hormone expression in a neuronal cell line - PubMed
The...
Anyone has the full text of this paper?
Roles of POU3F2 in Brain Development and Neuropsychiatric Disorders
Roles of POU3F2 in Brain Development and Neuropsychiatric Disorders - Liu - 2026 - Developmental Neurobiology - Wiley Online Library
The prioritzation of FBXL4 in the preprint seems to be mostly based on it being the closest gene. But it is not really close and the 3D chromatin data suggested a link with POU3F2 which is also the strongest brain-based protein coding gene nearby.
So my guess for this locus is that it points to...
Here are the results of my brief analysis of this locus (there's more about my methods and approach in the chr20 locus).
Credible set
This region also had one credible set of 86 SNPs over a 180 kb. It’s in a gene desert, far removed from protein coding genes but lies in a long non-coding RNA...
New breakthroughs on:
Local smoothing and the Kakeya conjecture
The Exponential Time Hypothesis is talse
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Would be interesting in hearing...
I had a closer look at this locus using the methods I previously applied to chr20 and other loci. No breakthrough unfortunately, but I’m sharing my results in case they are useful to others.
Finemapping
Finemapping the locus with SUSIE gave one credible set with 92 SNPs. But ca. 80% of the...
I agree that there's a lot of uncertainty in the chromatin and histone mark data (the databases are still too small and don't cover enough situations and context), but genetics mostly point to risk factors. So it's about how you get ill when you don't have ME/CFS yet. And these genetic hits all...
I think the gut diseases like IBS are interesting because CA10 isn’t expressed in the gastrointestinal tract. So that likely points to the specific neurons linked to the stomach and gut being involved in these diseases through CA10 (over?)expression. On the other hand, it’s interesting that...
Predictions
The AlphaGenome gave no valuable results or insights.
eQTL
Also, no real matches in the eQTL datasets. The best I found for CA10 was a weak signal in serotonergic neurons (PP.H4 = 0.365, lowest p = 1.7e-3). It does give some info about the direction of effect. If this signal is to...
I did the same analysis as for the chr20 region. Finemapping with Susie gave a credible set with 64 SNPs that is hard to reduce to a smaller number: the probability is spread out across these SNPs. CA10 is the only protein-coding gene nearby but a lncRNA called ENSG00000310017 falls inside our...
Interesting presentation during the PRIME symposium by Matthias Wielscher. He only talked about this briefly but it looks like his team did a n analysis of rare variants (so similar to the Astrazeneca data that highlighted BTN2A1) using All of US and the UKBiobank cohorts.
The All of us Cohort...
Thanks, sounds interesting although I didn't come across strong signals to T-cells in the chromatin data so am a bit skeptical about this line of thinking. Would like to get more detail about the graphs shown during the presentation.
Chris Ponting also presented a T-cell theory based on the...
Yes I think that's the case for this locus on chromosome 20. It's all still speculative. But I plan to do similar analyses on the other signals and then see if any patterns or links emerge.
If we test gene categories across all the DecodeME results then they point to the CNS and neuronal...
ARFGEF2 could be the gene for this link because mutations have reported "preferential damage to the basal ganglia" and "hyperintensity of the putamen" which was associated with movement disorders.
Some references:
Movement disorder and neuronal migration disorder due to ARFGEF2 mutation - PMC...
Regarding the direction of effect, it seems that the ME/CFS risk alleles are associated with lower cortical volume, increased risk of schizophrenia but decreased risk of bipolar disorder. That study thought that CSE1L is the most likely candidate gene based on eQTL data.
Genomic Dissection of...
I noticed that in the Astrazeneca analysis of rare variants, multiple ME/CFS categories have PREX1 (a candidate gene in this region), around p = 10^-4. Not really close to significance, but perhaps it's a valuable signal.
AstraZeneca PheWAS Portal
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