USP18 is a negative regulator of interferon response, which suggests that the variant increases SLE risk by affecting USP18’s ability to limit the interferon response

Congratulations to the team on this work!

They found an interesting variant in the USP18 locus: a trans-eQTL that increases the expression of 50 interferon response genes. This variant also colocalises with a GWAS signal for systemic lupus erythematosus (SLE)

This release also features:

➡️ molQTL credible sets for targets
➡️ new options for the variant structural viewer
➡️ data updates from GWAS Catalog, Expression Atlas, gnomAD, DepMap, and Probes&Drugs

What do you think of this update?

@riyavsinha.bsky.social @jengreitz.bsky.social sky.social @anshulkundaje.bsky.social y.social have made the ENCODE-rE2G data available to browse through the E2G portal, a custom-built extension of the Platform 👇

We plan to further integrate their data 👀

e2g.stanford.edu

This new data can provide insights about the function of genetic variants by linking them to likely regulatory elements that affect the transcriptional activity of nearby genes, and is available to browse on our variant pages

This is fantastic — congratulations @gwascatalog.bsky.social!

The authors suggest that small molecule inhibition of LRRK2, or reduction in LRRK2 protein levels, may help slow the progression of diseases involving tau or alpha-synuclein, such as Alzheimer’s and Parkinson’s disease.

Congratulations to the whole team for this work! 🎉

The study revealed that LRRK2 was required for the uptake of tau and alpha-synuclein, and that the LRRK2 Parkinson’s disease gain-of-function mutation increases the uptake of both forms of tau and alpha-synuclein.

They found that monomeric and fibrillar tau are taken up by neurons in overlapping but distinct pathways.

Using genome-wide CRISPR knockout screens, the team delineate the genes required for extracellular uptake of monomeric and fibrillar tau in human iPSC-derived excitatory neurons, the primary cell type affected in tauopathies.

Several neurodegenerative diseases are characterised by the formation fibrils of misfolded tau protein, and it is thought that disease progresses through the central nervous system from affected neurons releasing pathogenic forms of tau protein, which are then taken up by neighbouring neurons.