I have now spent almost four months to get this paper with @ericfauman.bsky.social desk-rejected from three journals (Genetic Epidemiology, eLife and HGG Advances) and not really sure where to go from here. www.medrxiv.org/content/10.1... - ThreadSky

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kauralasoo.bsky.social • 14 days ago

I have now spent almost four months to get this paper with @ericfauman.bsky.social desk-rejected from three journals (Genetic Epidemiology, eLife and HGG Advances) and not really sure where to go from here.
https://www.medrxiv.org/content/10.1101/2024.10.21.24315891v2

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kauralasoo.bsky.social•14 days ago

We explore how to make reliable causal inferences if the traits that we have measured (such as plasma metabolites) are indirect biomarkers that are unlikely to have a direct causal effect.

kauralasoo.bsky.social•14 days ago

We propose that instead of making inferences about the molecular traits themselves (i.e. does increased plasma histidine have a caual effect on vitamin D), we can use molecular traits as proxy readouts for protein function.

kauralasoo.bsky.social•14 days ago

The question then becomes: does increased HAL protein activity (proxied by reduction in plasma histidine) have a causal effect on vitamin D? Turns out that this is feasible, but only if certain assumtions are satisfied.

kauralasoo.bsky.social•14 days ago

Our core idea itself is not particularly novel and is closely related to drug-target MR (see e.g. this review by @stevesphd.bsky.social: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-024-03700-9), but I do think that the two case studies that we present are quite insightful.

kauralasoo.bsky.social•14 days ago

Any editors out here who would be interested in reviewing it?

stevesphd.bsky.social•13 days ago

Sorry to hear, and hope this piece finds a nice home! Agree that, particularly for drug development, thinking of risk factors as biomarkers for underlying mechanisms is the right way to conceptualize the genetic associations - the risk factor doesn't not have to be the literal causal factor.

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