A cis-eQTL in AHI1 confers risk to schizophrenia in European populations

Schizophrenia is a devastating mental disorder, with heritability as high as 80%. Although genome-wide association studies have identified multiple promising risk variants of schizophrenia, they could only explain a small portion of the disease heritability, and other variants with low to moderate effect remain to be identified. Abelson helper integration site 1 (AHI1) is highly expressed in mammals throughout the developing brain, with lower expression continuing into adulthood. Besides, previous evidence suggested that AHI1 expression was changed in schizophrenia patients. Furthermore, association signal between AHI1 variants and schizophrenia has been reported in several European samples. In the present study, we first analyzed two expression quantitative trait loci (eQTL) datasets in healthy individuals and investigated the associations of eQTL of AHI1 with schizophrenia in independent European samples. We observed that a cis-eQTL of AHI1, rs11154801, showed significant association with AHI1 expression in both datasets (P < 5E-05). Genetic evidence exhibited that rs11154801 was significantly associated with schizophrenia risk in both the discovery sample (9394 cases and 12462 controls, P = 0.046, OR = 0.958, 95% CI = 0.918-0.999) and the replication sample (3240 cases and 14786 controls, P = 0.024, OR = 0.949, 95% CI = 0.870-0.990). When the discovery and replication samples were pooled together, this association was further strengthened (P = 0.004, OR = 0.949, 95% CI = 0.916-0.983). These results suggested that AHI1 is likely a risk gene for schizophrenia, at least in European populations.