@sanogenetics @doctorveera would love to hear any thoughts you have on this. Your podcasts and blogs have been a great source of information.

Naive population genetics question: in multi-ancestry GWAS, are ancestry-specific associations common? For example, the recent BD analysis from @PGCgenetics found EAS specific associations. Rule or exception? @SashaGusevPosts @dgmacarthur @tuuliel https://t.co/grKwq1WMdY

Excellent write up by @doctorveera found here: https://t.co/A4xc1gYfzw

A new paper has identified an answer to this question, in which a structural variant causes the de novo creation of a cardiomyocyte-specific enhancer, leading to ectopic expression of a potassium channel and heart disease.

A big congratulations to our #GWAS24 Poster Winners, Luis Eichelmann (@LuisEichelmann) from @UniLuebeck & Brandon Logeman (@brandon_logeman) from @Harvard 🎉👏

New GWAS study examines when a baby takes their first steps 🧬 ➡️ 🚼 ➡️ 🚶‍♀️ SNP based heritability, a lower bound of heritability calculated using only common variants, shows up at ~25%, much higher than I would have guessed. Work led by @annagui86

If you've made it this far thanks for reading and here again is the link to the original paper. https://t.co/Y7FlnVj58D

Finally, the clever use of a disulfide linker enables the two molecules to dissociate upon entry into the reducing environment of the cytoplasm. This strategy could further be used to deliver non-cell permeable reagents to cell types of interest.

3) NMDA receptor antagonist. By using the cell-targeting strategy one can deliver these antagonists, which have already been shown to reduce food consumption, to circuits of interest to avoid the previously observed side effects.

2) Cell-type specific targeting. By using the Glp1 neuropeptide as a building block, one can add an additional chemical moiety that will be delivered to Glp1 receptor expressing cells.

1) Glp1 agonists have shown remarkable results in lowering body weight and have become immensely popular among individuals seeking to lose weight. This new bifunctional molecule builds upon these results.

Which is why the authors fused an existing NMDA receptor antagonist with the now widely popular neuropeptide Glp1. This creates 3 key features for this application:

But due to brain wide expression of NMDA receptors multiple neuronal circuits are affected, leading to a significant side effects...

Previous work had shown that injecting NMDA receptor antagonists into the lateral hypothalamus inhibits food intake and causes a reduction in body weight. https://t.co/M2qugqugaV

"...our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation..." https://t.co/Y7FlnVj58D

Targeting 💊 to specific cell types in the brain is challenging, but this new paper uses a bifunctional molecule that delivers an NMDA receptor antagonist to GLP-1 receptor expressing neurons in an effort to treat obesity 🧵

I’m looking for examples where a gene is normally expressed in cell type A but a GWAS/QTL hit contains a variant that causes ectopic expression in cell type B. All examples welcome, plz RT! @jkpritch @doctorveera @SashaGusevPosts @dgmacarthur @tuuliel @anshulkundaje

In a G0 cell, if Cohesin is continuously chugging along performing loop extrusion it must be going through a large amount of ATP. Does anyone have an idea how much of the cellular energy budget is dedicated to this process? @job_dekker @Jesse_R_Dixon @Anders_S_Hansen

Several colleagues have asked for our protocol for preparing low-input samples for single nucleus multiome (gene expression + ATAC) sequencing. It is now available on @STARProtocols ( https://t.co/ozwW4SOWkP) so that everyone can give it a try. 1/7

Suprachiasmatic nucleus promotes hyperglycemia induced by sleep delay: Current Biology