Methylome-wide association studies of traumatic injury identifies differential DNA methylation of synaptic plasticity and GABAergic-signalling.

Traumatic physical injury is often associated with psychological trauma and is a risk factor for major depressive disorder (MDD). In Generation Scotland traumatic injury was significantly associated with recurrent major depression (OR = 2.10, 95% CI 1.33-3.33, PLJ=LJ0.0016). and schizotypal symptoms, particularly disorganised thought ({beta}LJ=LJ0.111, 95% CI 0.049-0.177, PLJ=LJ0.0004). We performed methylome-wide analyses of traumatic injury in individuals with MDD and controls separately to investigate the link between traumatic injury and MDD. Nominally significant differences in differential DNA methylation between MDD and control groups were identified at 40 003 CpG sites (p 2, FDR q-values < 0.01). Enrichment analyses for regional brain-expression in the recurrent MDD group highlight the limbic lobe and supraoptic nuclei (recurrent MDD FWER = 0.028 and 0.034, respectively). These results suggest that traumatic injury is associated with patterns of DNA methylation differentially in individuals with MDD compared to controls, highlighting the need for novel analysis approaches.