Fig 1.
Illustration of the difference pathways which may be reflected by protein associations with genetic variables and disease liability.
Panel A shows the relationship between genetic variants (G1-9), upstream proteins (P1-6) and downstream proteins (P7-9) via the disease liability pathways. Panel B shows the relationship between SNPs and upstream protein P6. Panel C shows the relationship between SNPs and downstream protein P9.
Table 1.
Cancer frequency within the UKB cohort and within the UKB-PPP study participants.
Fig 2.
Directed Acyclic Graphs (DAGs) showing the three IV assumptions of Mendelian Randomization.
IV1 represents that the assumption that the genetic variant (G) is strongly associated (red arrow) with the exposure (E). IV2 represents the assumption that confounders don’t also act on the genetic variant (red dashed arrow) as they do the outcome. IV3 represents the assumption that the genetic variants do not affect the outcome through other routes separate from the exposure (red dashed arrow) (C).
Fig 3.
Flowchart of methodology and data selection.
UK Biobank data will be filtered based on exclusion criteria and availability of protein data, this will filter into proteins identified. Cis-pQTLs for the proteins will be identified which will either by used as instruments for forward MR or excluded from reverse MR. Various MR analyses will be performed based on number of SNPs available and sensitivity analyses will be used to filter proteins to perform colocalization.
Table 2.
Prevalent and incident cases of cancer from UKB cohort and within the UKB-PPP study participants.