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The meta-GWAS (DME_1 + MVP)

Wrote more about this here: The symptom signaling theory of ME/CFS involving neurons and their synapses | Science for ME Don't see the issue with triggering versus maintaining the disease being two separate problems. Suppose the issue is overfiring of a neural network involved in fatigue and...

It uses tools like MAGMA that convert SNP associations with ME/CFS into gene associations with ME/CFS. It doesn't only use the SNPs that reach significance but all the results for the millions of SNPs across the genome. It uses their p-value and combines them into a p-value for a gene. It does...

Dropviz This is the mouse brain atlas with RNA data from 0.69 million cells. The main publication is Saunders et al. 2018. but there's also a website with visualization and an option to download the data: http://dropviz.org/ The FUMA website has a pre-processed file that controls for the...

If I understand correctly layer 6A form a connection between the cortex and thalamus but perhaps also the claustrum and other inner structures. Layer 6A Pyramidal Cell Subtypes Form Synaptic Microcircuits with Distinct Functional and Structural Properties - PMC So one hypothesis for ME/CFS...

Using conditional analysis, three cell types remain as independent: - the striatal inhibitory medium spiny neurons, - the dentate principal cells in the hippocampus - the layer 6a cells in the posterior cortex.

Here's some more info on these cell types by matching them to the annotation file: ID Brain Region Common name cell_cluster GP.Neuron_Gad1Gad2-Th_Adora2a-Th.3_9 Globus Pallidus Striatum, Th+ SPN GABAergic STR.Neuron_Gad1Gad2_Drd1-Cxcl14.10_5 Striatum dSPN, lateral striatum GABAergic...

Level 2 Level 2 has 565 cell types. I've tried to deduce some info form the markers they have. For example: Gad1Gad2' = GABAergic, while Slc17a7 or Slc17a6 = Glutamatergic. There were significant hits for both. Here are the ID's of the 13 cell types that reached bonferonni-significance...

Level 1 Here's what I got for the level 1 classification which has 88 cell types. The results show again that only the neuron type reaches statistical significance. It's also clear that the signal isn't confined to one brain region. The signals in the cerebellum and substantia nigra look a...

I had a go at matching genetic data on ME/CFS with the gene expression data from Dropviz. This is the paper that discovered the eccentric medium spiny neuron (discussed here). It's a mouse brain atlas with RNA data from 0.69 million cells. The main publication is Saunders et al. 2018. but...

The paper writes: Has anyone been able to find this appendix?

ImmGen data The Finucane 2018 paper also included an older version of the dataset on immune cells from the Immunological Genome (ImmGen) project. Immunological Genome Project Using LDSC, I got similar results to trafalmadorian97, with the top hit reaching a p-value around 0.005 for 292 cell...

Linnarson Mouse Brain Atlas This is an older Mouse Brain Atlas from the Linnarson lab at the Karolinska Institute (the same group that published the human brain atlas). The data from different dissections was spread out over multiple publications. Skene et al. 2018 and later Olislagers et al...

Yes, you reported it correctly, and thanks for clarifying. I just wanted to add that the Seeker white matter cells aren't seen as independent from the top Siletti eMSN signal if you follow the Watanabe 2019 approach (EDIT: ignoring the HEAL2 replication).

Background Had a closer look at the conditional analysis as specified by Watanabe et al. 2019. Step 3 is about checking if cell types from different datasets are independent of each other. The basic idea is that for each pair of cell types, you first do a MAGMA regression with one cell type...

A recent and useful lecture on the limitations of cell-type enrichment analysis with GWAS data. It's from Rachel Brouwer, a member of the Posthuma group that produced FUMA, MAGMA, FLAMES, etc. The conclusion is a bit sobering. These analyses work well for broad cell types (like neurons, glia...

These analyses were a bit above my level as an amateur so don't take them too seriously.

There is one caveat to this analysis, the olisalgers et al. 2021 paper found that this linear MAGMA analysis with quantiles performed worse (did not align with their other methods). They prefer LDSC or MAGMA with the top 10% of genes as binary annotation. They also restrict their GWAS to the...

The data is available in the R package MAGMA.celltyping by the authors. neurogenomics/MAGMA_Celltyping: Find causal cell-types underlying complex trait genetics Mouse gene have been mapped to human equivalents by them. They also changed the gene expression specificity into 40 quantile (I...

Another cell type study that I wanted to test the DecodeME data to. They used an older Mouse Brain Atlas from the Linnarson lab at the Karolinska Institute (the same group that published the human brain atlas). The data from different dissections was spread out over multiple publications such...