Indicators of HSV1 Infection, ECM–Receptor Interaction, and Chromatin Modulation in a Nuclear Family with Schizophrenia

Schizophrenia (SCZ) is a complex psychiatric disorder with high heritability; identifying risk genes is essential for deciphering the disorder’s pathogenesis and developing novel treatments. Using whole-exome sequencing, we screened for mutations within protein-coding sequences in a single family of patients with SCZ. In a pathway enrichment analysis, we found multiple transmitted variant genes associated with two KEGG pathways: herpes simplex virus 1 (HSV1) infection and the extracellular matrix (ECM)–receptor interaction. When searching for rare variants, six variants, SLC6A19(p.L541R), CYP2E1(p.T376S), NAT10(p.E811D), N4BP1(p.L7V), CBX2(p.S520C), and ZNF460(p.K190E), segregated with SCZ. A bioinformatic analysis showed that three of these mutated genes were associated with chromatin modulation. We found that HSV1 infection, ECM–receptor interaction pathways, and epigenetic mechanisms may contribute to the pathogenesis of SCZ in certain families. The identified polygenetic risk factors from the sample family provide distinctive underlying biological mechanisms of the pathophysiology of SCZ and may be useful in clinical practice and patient care.