Abstract Genome-Wide-Association studies have involved miR-137 in schizophrenia. However, the biology underlying this statistical evidence is unclear. Statistical polygenic risk for schizophrenia is associated with working memory, while other biological evidence involves miR-137 in emotion processing. We investigated the function of miR-137 target schizophrenia risk genes in humans. We identified a prefrontal co-expression pathway of schizophrenia-associated miR-137 targets and validated the association with miR-137 expression in neuroblastoma cells. Alleles predicting greater co-expression of this pathway were associated with greater prefrontal activation during emotion processing in two independent cohorts of healthy volunteers (N 1 =222; N 2 =136). Statistical polygenic risk for schizophrenia was instead associated with prefrontal activation during working memory. A co-expression pathway links miR-137 and its target genes to emotion processing and risk for schizophrenia. Low prefrontal miR-137 expression may be related with SCZ risk via increased expression of target risk genes, itself associated with increased prefrontal activation during emotion processing.

A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing