It is also anticipated that discovered associations that pass a threshold of required genome-wide statistical significance are likely to have observed effect sizes that are inflated compared with the true effect size [33]. Moreover, it is usually impossible to tell upfront whether a newly discovered genetic variant is the direct culprit or simply linked to the (yet unknown) causal variant. The analytical methods used, e.g. genetic model specification (or misspecification), may also affect the magnitude of the effect size. Finally, discovery of a genetic locus has important implications on its own, regardless of the observed effect size, e.g. it may highlight some interesting biological pathway and may give some insights into developing new therapeutics.
