association, a conditionally significant TWAS signal along with the finemapping evidence suggests that WDR6 is a causal gene at this locus, however, further analyses such as SNP based finemapping and in silico prediction of variants in this locus are warranted to confirm this finding given genetic influence on disease may not directly be mediated by cis-acting expression. WDR6 is a conserved repeat region expressed ubiquitously during human development that may function as a restriction factor to inhibit virus replication and a protein complex assembly platform (Li et al., 2000; Sivan, Ormanoglu, Buehler, Martin, & Moss, 2015; Smith, 2008). Previous work in a rodent model suggests WDR6 may modulate insulin signalling in the hypothalamus (Chiba et al., 2009), which is interesting given that we observed evidence to suggest fasting insulin level exerts a protective effect against AN risk (Adams et al., 2021).
