Table 1.

Genes with Gene-Based q < 0.05 for Negative (Top Panel) and Positive (Bottom Panel) Symptoms

Gene	Gene-Based P -Value	Gene/Protein Function	Additional Notes
Negative symptoms
NKAIN2	P = 7.35×10−7	Transmembrane protein that interacts with a Na+/K+ transporting ATPase	Previously associated with case–control status in a meta-analysis that included one of the current samples.41 That result was based on rs6917824 (P = .80 in current Neg results).
			Previously associated with cognitive decline in Alzheimer’s patients42 based on rs117780815 (P = .70 in current Neg results).
			Previously associated with neuroticism43 (all associated SNPs P > .7 in current Neg results). See text for additional details.
LSM6	P = 1.34×10−6	Involved in RNA processing	Perturbations of genes in the Lsm family have been associated with spinal muscular atrophy.
GLRA1	P = 2.01×10−6	Glycine receptor subunit; receptor mediates postsynaptic inhibition in CNS	Mutations can inhibit glycine signaling in the CNS. Mutations can cause hereditary hyperekplexia.44,45
G3BP1	P = 2.34×10−6	DNA-unwinding protein responsive to environmental stress46,47	No known previous associations with neurobiological or psychiatric phenotypes.
BCAT1	P = 2.92×10−6	Cytosolic form of transaminase; essential for cell growth	Cytosolic BCAT genes are expressed in GABA-ergic and glutamatergic neurons in the brain. These proteins potentially play a role in glutamate toxicity, which contributes to the development of some neurodegenerative disorders.48
Positive symptoms
KIAA1430	P = 3.23×10−7	Coding protein of unknown function	Flanked by SLC25A4 (P = 1.17×10−5, q = 0.06) and SNX25 (P = 6.15×10−5, q = 0.09). SLC25A4 encodes a mitochondrial ADP transporter that is responsive to escitalopram treatment in a mouse model of depression.49 SNX25 is expressed in neurons and astrocytes; its expression is increased in the temporal neocortex of patients with temporal lobe epilepsy.50
NRG1	P = 1.12×10−6	Encodes a glycoprotein that mediates cell–cell signaling; plays a role in growth and development of multiple organ systems; expressed in glutamatergic synaptic vesicles	Dysregulation has been previously associated with schizophrenia and bipolar disorder. See “Discussion” section for additional details.
PHACTR3	P = 6.39×10−6	Member of the phosphatase and actin regulator protein family	Encoded protein scapinin is preferentially expressed in the brain; has been shown to enhance cell spreading, potentially through the modulation of actin cytoskeleton structures.51 Some evidence suggests that scapinin has a regulatory role in neuroplasticity.52