TNFRSF21 (tumor necrosis factor receptor superfamily, member 21) was the closest (~34kb downstream) gene to eight intergenic SNPs reaching suggestive significance for psychological distress. Whereas TNFRSF21 presents as a good candidate gene for anxiety and depression—due to its role in inflammation and immune regulation—our SNPs were not in LD with SNPs in TNFRSF21. A SNP located in NOS1 (encoding nitric oxide synthase 1) was suggestively associated with psychological distress, but unlike the SNPs located near TNFRSF21, this SNP showed no association with anxiety/depression symptoms. In rodent models of stress, nitric oxide levels in plasma and brain affect stress-induced neurobehavioural measures and stress susceptibility (Gilhotr et al. 2010). In humans, haplotypes in NOS1 have been associated with suicidal behaviour (Rujescu et al. 2008).
