chr1swallace/coloc

Questions about the coloc hypotheses

mocksu opened this issue · 0 comments

mocksu commented

For coloc, we have 5 competing hypotheses:

H0: no causal variant
H1: causal variant for trait 1 only
H2: causal variant for trait 2 only
H3: two distinct causal variants
H4: one common causal variant

What I have in mind for trait 1 is "expression level of gene A", for trait 2 is "breast cancer".

H0 is easy to understand: the genomic region interrogated has nothing to do with trait 1 or trait 2.

H1 is a little harder. First I thought I understand it, but now I am not sure. Does it really mean there is a variant in the underlying genomic region that is causing (NOT being associated with) the changes in expression level of gene A? First I thought it merely suggests association instead of causality here, but the "causal" in "causal variant" puts me to rethink.

H2 similar to H1.

H3 & H4 are quite confusing. To make my questions clearer, please take a look at the figure below (Verena Zuber 2022)

image

Guess my questions could be simplified to:

  • which plot in the above figure corresponds to H3 and which plot to H4?
  • May I guess B corresponds to H4? A to H3?
  • How about plot C, D, and E? Are they tested as well?
  • Which hypothesis is equivalent to "The change of gene A expression level causes the change of risk of breast cancer"?
  • Which plot describes the scenario of "The change of gene A expression level causes the change of risk of breast cancer"? C & E?

Thanks so much in advance!