Ian McDowell, Athma Pai, Cong Guo, Christopher M Vockley, Christopher D Brown, Timothy E Reddy, Barbara E Engelhardt
Interesting paper! The Mendelian Randomization approach is quite clever.
Had a couple thoughts:
I like the idea of using SNPs to infer expression level and then look for changes in transcription, and I agree that it removes the "shared confounder" issue. However, I'm not sure it necessarily proves the case for a trans interaction. Let's say lincRNA A causes mRNA B (which is closeby, hence in cis) to change expression, which in turns causes distal mRNA C to change expression. Then, the mechanism is in cis, but the effect is in trans, right? I get that the cis changes didn't show up, but it is possible that the effects were below the detection threshold. Am I missing something?
For those of us, umm, naive to the "naive" approach, the description was rather opaque. Is there a more plain English description of how the naive approach works and thus how it differs from Mendelian Randomization?
Anyway, cool work!