Hi all,
I have a question about the direction of effect in polygenic risk scores. An illustrative example:
GWAS data:
snp maj/min OR
rs11884770 C/T 0.98
In my VCF file (same genome build as the above):
snp ref/alt
rs11884770 T/C
So in this case, the reference allele is the "effect" allele (T), and that effect is negative. My naive understanding is that I should simple count the number of Ts in this case, and then weight this in the negative direction by multiplying by log(0.98) = -0.0202.
But I read somewhere else that it's correct to count the Cs (as this is the "risk" allele in this case) and invert the direction of effect. Which is correct? I do note that many scores in prscatalog report plenty of negative weightings, which suggests that my original idea is right?
Many apologies if this is confusing - I have confused myself thoroughly also.
