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I made a thread with some papers about TWAS: https://www.s4me.info/threads/a-gene-based-association-method-for-mapping-traits-using-reference-transcriptome-data-2015-gamazon-et-al.48810/

The aim of TWAS is to help identify the consequences of genetic variation in a GWAS on gene expression, which could help identify genes and tissues that may causally influence the disease. The basic steps of TWAS 1. First, a prediction model is created using data from large reference datasets...

The results reported from doing a transcriptome-wide association study (TWAS) based on depression GWAS data made me interested in learning more about TWAS. The abstract above is from the paper that introduced the first form of TWAS, PrediXcan. The first paper below introduced S-PrediXcan, a...

A gene-based association method for mapping traits using reference transcriptome data Abstract Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in...

I agree with that last sentence that this seems to be a remarkable finding and supports the potential of GWAS and TWAS, because a decrease in dopamine receptors in the nucleus accumbens seems to be exactly what you would expect to be implicated in depression. DRD2 in nucleus accumbens was...

They looked for drugs that might target the depression-associated genes. It might be an interesting technique to use for ME/CFS genes. Discussion about some of these drugs:

Just copying the top enriched gene sets. It's basically synapse-related.

They talk about one area that might represent such a neuropsychiatric common component: Edit: 3p21 covers a wide area. Here's that range plotted with DecodeME data: A couple small spikes, but not significant.

MAGMA gene set associations: I thought the B cell mention might be interesting.

It seems like the most significant hit from the anxiety study image above is GABAergic neurons in the midbrain, not cortex.

Actually, maybe I can do a very simple version. Just checking if specific variants from DecodeME are associated with tissue expression in GTEx. The top variant in the NEGR1 locus is 1:73126414:C:CA (rs34330896). Here's the page for that variant on GTEx...

No, they didn't look at gene expression linked to the SNPs near NEGR1 because that locus didn't quite reach genome-wide significance. I think it might be doable with the freely available DecodeME data by someone who knows how, but I don't think I have the knowledge or energy to do so.

Ha maybe. Though GTEx probably gets a lot of funding because the data can then be used by any other GWAS studies in any diseases, to try to see if results line up with gene expression - as it was used here, and as it was used in DecodeME, for example.

The expression data for hypothalamus, and all other tissues, is from an existing database of variant-expression associations, GTEx. There was no new testing of gene expression in this study, if that's what you mean. From GTEx: So the question they're trying to answer, basically, is "do the...

It wasn't done in the DecodeME paper, though it was attempted by me. It seemed to point to neurons all over the brain (excitatory, "GABAergic", and just "neurons"). I'm hoping they do something like this in the final paper. Edit: Cell types from this study: Edit: Note that the analysis I did...

Yeah, it's possible. It's more meant as one piece of evidence. If the GWAS points to a gene's expression in one specific tissue, and other evidence implicates the same tissue, it adds to the evidence. Though, it could be that a hypothalamus association might just exist due to similarity of...

Considering that this GWAS has many different anxiety phenotypes combined together, and considering the overlap with DecodeME in MAGMA, my suspicion is that this may be getting to a "root" specific component that all these diseases, including ME/CFS might have in common. Maybe further very...

To add to the above post, they are looking for how well SNP associations match with gene expression in specific tissues. Like DecodeME did using a different method, where they found, for example, that ME/CFS SNPs matched up with expression of RABGAP1L expression in several specific tissues.

A transcriptome-wide assocation study (TWAS), used here, does something like trains a machine learning model to predict expression of a given gene based on SNP patterns (using existing expression databases like GTEx), then uses some method (that I don't really understand) on GWAS summary...

2021 study, but I was interested in it because it's so large (>350,000 cases), and to see how the MAGMA tissue enrichment might compare with DecodeME or a large anxiety GWAS, which seem to have similar MAGMA results. Here is the MAGMA tissue enrichment from this study: In order of...