Fig. 5: Genetically predicted GRK3 expression, KYNA levels, and psychotic symptoms in humans.
From: GRK3 deficiency elicits brain immune activation and psychosis
The SNP rs478655 (MAF: 0.29) was used to represent a cis acting eQTL in the GRK3 promoter with TT genotype denoted as high GRK3 RNA expression (black circle), CT as medium GRK3 RNA expression (gray circle), and CC as low GRK3 RNA expression (white circle). A CSF levels of KYNA, in a sample of 48 healthy individuals, as a result of genetically predicted GRK3 RNA expression (β = 0.051, P = 0.026). B Distribution of subjects with high, low, and medium prediction scores for GRK3 RNA expression in a sample of 70 bipolar disorder subjects. Subjects with a history of psychosis had higher predicted GRK3 RNA expression (OR = 2.6; 95% CI: 1.09–6.16). C Lack of GRK3 prevents internalization of microglial and/or astrocytic P2X7R, thereby triggering caspase-1 to produce IL-1β. This cytokine induces the kynurenine pathway, resulting in increased production of KYNA, a neuroactive compound that facilitates dopamine neurotransmission. All tests were two-tailed.
