The genome-wide significant locus we identify to be associated with anorexia nervosa is broad and multigenic (chr12:56,372,585-56,482,185). Mechanistic explanations about the role of the associated variant require additional functional data; nevertheless, we note the possible role for genes at this locus in the pathophysiology of anorexia nervosa. PA2G4 is involved in growth regulation and acts as a corepressor of the androgen receptor (35). ESYT1 [extended synaptotagmin-1 which binds and transports lipids (36)] is enriched in the postsynaptic density, which is implicated in the etiology of schizophrenia (37). Perhaps more convincing is that the sentinel marker for this locus, rs4622308, is in high LD with a known GWAS hit for type 1 diabetes (20), and rheumatoid arthritis (21), and the region around it harbors multiple other autoimmune associations. Multiple reports of shared effects between anorexia nervosa and immune phenotypes fit into a broader pattern of above-chance comorbidity across psychiatric and immune phenotypes (38, 39). Evidence suggests that this shared risk is at least partly genetic in origin (23, 39). A negative genetic correlation between anorexia nervosa and rheumatoid arthritis was previously reported (23), and our LDSC estimate—though only nominally significant—is in the negative direction as well (see Supplementary Table S5).
