ERAP1 and ankylosing spondylitis: Examples of how identifying instances of epistasis affecting particular phenotypes can improve our understanding of the biological pathways that underlie them include the interaction between ABO and FUT2 affecting alkaline phosphatase (ALP) levels, which reflects a known functional interdependence between ABH secretor status, ABO blood type and intestinal ALP [10, 18, 19], or that between an ERAP1 variant and the HLA-B27 allele for ankylosing spondylitis risk, informative about disease mechanism since the ERAP1 enzyme is involved in peptide trimming for HLA presentation [9].