Fig. 6. Imagined case in which independent loss-of-function (LoF) alleles give rise to adaptive dwarf phenotypes inspired by (Barboza et al. 2013).

In this case, a premature stop codon and a frameshift mutation have arisen in alternative genetic backgrounds distinguished here by a nearby SNP (top). Conventional, functionally agnostic GWAS (bottom left) tests for association between individual variants and the trait of interest, in this case plant height, fail because none of the individual variants capture the functionally definitive variation (indicated by p-values below the significance threshold marked by the dashed line). An alternative approach, functional GWAS, first annotates variants according to predicted functional effects, then defines alleles as functional or non-functional. This corrects for allelic heterogeneity when testing for allele-trait associations and results in a significant allele trait association (bottom right).