Getting signs of GWAS effects relative to major alleles instead of alt alleles

Feature requests
1

Have there been past discussions on how to get GWAS effect signs for major alleles using data already in Open Targets?

I see https://genetics-docs.opentargets.org/faqs#what-is-the-alternative-allele-why-not-use-the-minor-allele, specifically the section on preferring alt alleles over minor alleles and it makes sense. Nevertheless, I would like to be able to interpret effect signs according to population frequency instead.

Is there existing code for doing this somewhere in the OT ecosystem? Or is this rarely asked for?

2

Any chance somebody could reclassify this as a feature request for me? @Prashant_Uniyal or @dsuveges perhaps? Sorry, I’m realizing now that would have been a better category for it.

I’d like to reclassify Inferring direction of therapeutic effect implied by coding genetic evidence that way too if possible.

3

Hi Eric,
i have reclassified both messages as “feature request”.
Thank you for your contribution!

Annalisa

4

Thanks @Annalisa_Buniello!

5

Hi Eric, it is also possible to perform a join between your variants of interest with the variant table from bigquery, or the variant index table from ftp , these tables have a nested column of the effect allele frequencies within the major ancestries from Gnomad. As the beta signs have been harmonised with respect to the alt alleles, they can then be flipped according to their allele frequencies to obtain their directionality with respect to the major alleles.

Hope that helps,
Xiangyu

6

Thanks @Xiangyu. Has it been requested before to be able to see effects harmonized to minor/major alleles in the genetics UI instead of ref/alt? I think that would be useful, though admittedly much less so outside of variants with clear causal impacts on a gene/protein.