Genetic overlap between schizophrenia and height implicates pituitary and immune response

Abstract

Shorter stature has been phenotypically linked to increased prevalence of schizophrenia (SCZ)1. Using genome-wide genetic data, we studied the SCZ-height relationship on a genetic level. We identified 22 independent lead SNPs (55% sign-concordant) and 142 genes statistically associated with both SCZ and height. Additionally, we found gene enrichment for pituitary cell-types and immune response gene-sets. While the global SCZ-height genetic correlation was nonsignificant, 9 genomic regions showed robust local genetic correlations (7 negative, 6 in the MHC-region). The shared genetic signal for SCZ and height within the 6 MHC-regions was found to be partially explained by mutual genetic overlap with serum white blood cell count, particularly lymphocytes. Fine-mapping prioritized 3 shared effector-genes (GIGYF2,HLA-C, andLIN28B) involved in immune response and developmental timing. Overall, the results illuminate the genetic processes involved in the SCZ-height relationship and illustrates the utility of genetic data in furthering epidemiological insight.