Association of Whole-Genome and NETRIN1 Signaling Pathway-Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank

Abstract

BACKGROUND: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genonnic-PRSs), were associated with white matter microstructure.