This may sound stupid, but I do have questions.
1. GWAS is based on the linkage disequilibrium between common SNP tag and potential causal alleles. Rare variants are not usually in LD with the tag. Is this correct?
Is it possible that rare variants can also be LD with those low-frequency SNP tag? Maybe SNP array only include common tag?
2. Since it's in low-frequency, of course compared with those common ones, it may need large effect size, or large sample size to reflect the effect of the rare variants. Is this correct?
I think it should be the discrepancy of allele counts between case and control that determines the odd ratio. Maybe for some rare variants, it's totally absent in control, though it's rare in cases, which still produce a large odd ratio.
Anyway, can GWAS detect rare variants?