Do psychiatric GWASs find drug targets? Excited to see our work linking GWAS and pharmacological treatments in psychiatric disorders now published in JAMA Psychiatry jamanetwork.com/journals/jam... 🧬💊🎯 Big thanks to @bendfulcher.bsky.social @alexfornito.bsky.social Mark Bellgrove 🧵👇 - ThreadSky

Do psychiatric GWASs find drug targets?

Excited to see our work linking GWAS and pharmacological treatments in psychiatric disorders now published in JAMA Psychiatry https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2827732
🧬💊🎯

Big thanks to
@bendfulcher.bsky.social
@alexfornito.bsky.social
Mark Bellgrove

🧵👇

Comments

aurinaarn.bsky.social•16 days ago

1/6 GWASs were expected to inform the development of pharmacological treatments, such that identifying genetic variation associated with the disorder would provide targets for drug action. However, the direct translational applications have not yet been developed.

aurinaarn.bsky.social•16 days ago

2/6 Psychiatric disorders (most having a developmental component) present a special case, where the genetic risk that creates a vulnerability to illness may be distinct and separated in time from the pathophysiological mechanisms that influence symptom onset and severity.

aurinaarn.bsky.social•16 days ago

3/6 Here we integrate different functional information from protein-protein interactions, expression quantitative trait loci (eQTL), and spatial gene expression to determine the correspondence between GWAS hits and the genes for current drug targets.

aurinaarn.bsky.social•16 days ago

4/6 We propose a robust and realistic null model for significance testing that expects the identified matches to be specific for the selected group of treatments. Meaning that treatments for a selected disorder are expected to exceed matches for other treatments.

aurinaarn.bsky.social•16 days ago

5/6 We show that incorporating information derived from functional bioinformatics data, such as the PPI network can reveal links between GWAS and drugs for some disorders (bipolar disorder and diabetes [used for comparison]).

aurinaarn.bsky.social•16 days ago

6/6 But the correspondence for most other psychiatric disorders rarely exceeds null expectation suggesting that the genetic mechanisms driving the risk for psychiatric disorders may be distinct from the pathophysiological mechanisms targeted by drugs.

wiringthebrain.bsky.social•16 days ago

So, the answer is "no", right? "the genetic architecture driving the risk for psychiatric disorders may be distinct from the pathophysiological mechanisms currently used for targeting symptom manifestations through pharmacological treatments"

aurinaarn.bsky.social•15 days ago

According to our analysis and null model (which is quite stringent, but allows to ask a reasonable question) -- only in special cases, e.g. bipolar disorder. Matches for other disorders are very limited if any.

Comments

Posting Rules

Reply