How to handle GWAS catalog conflicting result during integration to OpenTargets?

Dear Team,

I notice there are lots of conflicting result between peak variants in the Association table and full summary statistics. I am curious Is there any similar situation happened when OpenTarget team integrate GWAS catalog data to the system?

For example, I noticed that some of the P-values for the peak variants in the Association table are inconsistent with the P-values in the corresponding full summary statistics (they can differ by several orders of magnitude). Also, some more significant variants near the peak variants are not included in the association table.

I’ve looked at this issue in 3 different studies that I’m interested in, so it doesn’t seem to be an isolated case. I’m curious what kinds of detailed processing might be happening between these two data sources.

To give an example, in this study (GWAS Catalog), rs7608892 vs. HDL is shown as 2e-12 in the table, but it’s 1.7e-15 in the downloaded summary statistics. And there are several nearby variants with p-values ~e-16 and LD with rs7608892 <0.3.



Dear Shicheng,

Welcome back! We have missed you! Hope you have enjoyed the summer and holidays!

Regarding the differences in P-values, the most likely explanation is that the P-values on OTG are the conditionally independent summary stats from GCTA cojo, where as the P-values on GWAS catalogue are not.

Best wishes,