Search results for query: NEGR1

I don't think this is 'just' clutching at straws. It is a very uncertain relation to NEGR1 but the p value threshold for the GWAS, as I understand it, has to be set high for multiplicity reasons and there are going to be lots of type 2 errors missing genuine links. I think the odds of there...

Could you spell this out a bit more for my slow brain: Are you saying you looked around NEGR1 and found DecodeME hits (ie. SNPs with relatively low p-value?) in locations where it would make sense for a promotor or enhancer to be, though none have been identified there yet by researchers?

...game we played here was telephone rather than straws. I think how we got here is forestglip made a post early on in the DecodeME thread about NEGR1, noting it was the closest gene to this SNP. Once NEGR1 popped up in a couple other GWAS I guess it sounded interesting enough to make a thread...

And so people are assuming that those hits between 73.00 and 73.50 are affecting the expression of the NEGR1 gene. How much of a long shot is that? Is it just clutching at straws? Is it at least as likely that the hits are affecting other genes? For example, KRT8P21 is in that range of peaks...

That plot includes lots of non-coding RNA. This one shows NEGR1 and LRRIQ3 are the closest coding genes to this locus. NEGR1 is interesting because there seems to be growing evidence that it is relevant in depression and anxiety disorders, though it seems like the causal variant is different...

Seems like NEGR1 was mentioned in a Depression GWAS. I think it was even less than 'the locus didn't quite reach genome-wide significance' in DecodeME. If we are going to look at genes with hits with a p value y axis of 4 or more, I think we'll be considering a very large percentage of human...

Remind me, why are we interested in NEGR1? It doesn't look very relevant from that DecodeME plot.

From my understanding a connection between NEGR1 and CD36 exists. https://pubmed.ncbi.nlm.nih.gov/35526561/ Interestingly, CD36 was mentioned by Hanson at this post by @Hutan...

...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 almost the most significant, but NEGR1 in the hypothalamus took the top spot. Top genes in each of the tissues they did TWAS on (reformatted):

...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: https://www.gtexportal.org/home/snp/rs34330896 There are only...

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.

So do we have any information about the possible link to NEGR1 in ME/CFS in terms of where the relevant (different) SNPs would have altered expression. I am doubtful one could draw any sensible conclusion but it might be interesting. I am sorry that I cannot keep up with the detail of the...

...in this study, if that's what you mean. From GTEx: So the question they're trying to answer, basically, is "do the SNPs associated with depression in this study match up with the SNPs associated with expression of NEGR1 in the hypothalamus (and all other genes and tissues) in the GTEx study?".

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...

But «exists in this tissue in general» is not the same as «is pathological in this tissue»? What if the pathology is in a different tissue where NEGR1 is also expressed?

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...

So how do they link the NEGR1 genetic linkage specifically to hypothalamic expression? That is what I am confused about.

I am not sure how they established that NEGR1 expression in hypothalamus and DRD2 in nucleus accumbens was relevant.

...ancestry (n=59,600; 25,843 cases). Transcriptome-wide association study (TWAS) analyses revealed significant associations with expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. 178 genomic risk loci were fine-mapped, and we identified likely...