Table 2.

Selected examples of transcripts differentially expressed (FDR ≤0.05) by affection status

Gene(s) Abbreviation	Comments	References
B3GNT2	A genome-wide significant association with rheumatoid arthritis has been reported, along with a less significantly association with Graves’ disease.	(49,80–84)
BCL2L2, BIK	These genes are involved in apoptosis; BCL2 itself (not differentially expressed) plays a crucial role in adult mouse hippocampal neurogenesis.	(131–133)
CYBB	A mouse knock-out prevents the typical behavioral and neurochemical abnormalities acutely induced by subanesthetic ketamine (which induces schizophrenia-like psychotic symptoms in humans).	(134,135)
DBNDD2	Dysbindin domain containing 2 mediates neural differentiation and apoptosis, and dysbindin itself (not differentially expressed) has long been of interest in schizophrenia.	(106,107,136)
DBP	This is a transcription factor involved in the regulation of some circadian rhythm genes, and has shown potentially relevant findings of interest: (i) reduced expression in fibroblasts from bipolar disorder subjects (it is downregulated in our case LCLs), (ii) induction in rat prefrontal cortex upon methamphetamine stimulation and (iii) is among the top findings in a combined sample GWAS for bipolar disorders.	(54,137–139)
DICER1	This gene is central in biogenesis of miRNAs. It is upregulated in the dorsolateral prefrontal cortex of schizophrenia cases (and in our case LCLs), and has important roles in normal central nervous system development and function, including that of dopaminergic neurons.	(86–92)
ELK1	This transcription factor has been reported as showing increased protein expression in the cerebellar vermis of schizophrenic subjects (also upregulated in case LCLs).	(140)
FAM69A	This is a member of a FAM69A-EVI-RPL5 gene cluster implicated in the autoimmune disorder multiple sclerosis by GWASs, and had some association support in the MGS EA GWAS.	(10,141–143)
GBP2, GBP4	These proinflammatory guanylate binding proteins (both upregulated in case LCLs) are induced by interferon and important for host defense against intracellular pathogens.	(144,145)
GLO1	This enzyme protects against glycation by catalyzing the conversion of reactive, acyclic alpha-oxoaldehydes. It has been previously implicated in autism and schizophrenia, and shown to be protective in a mouse model of Parkinson's disease.	(146–149)
HERC2	A homozygous missense mutation (Pro594Leu) in this gene is associated with a phenotypic triad of nonsyndromic intellectual disability, autism, and gait disturbance in three sibships.	(150)
HIST1H2BD, HIST1H2BC, HIST1H2BH, HIST1H2BG, HIST1H4K	These histones are all located in the xMHC region (which contains the most significant and best replicated GWAS association for schizophrenia). Histones have some antimicrobial activity especially lysine-rich histones, participate in the innate defense system of the human placenta particularly histone H2B (which is also found in the cytoplasm and in amniotic fluid), and there are previous reports of histone expression dysregulation in schizophrenia, Huntington's disease, and autism controls versus cases.	(10–13,37–41,46–48)
HNMT	This enzyme metabolizes histamine in the brain, and has been implicated in alcohol dependence (association of Thr105 functional variant with higher enzymatic activity) and Parkinson's disease (association of Ile105 functional variant with lower enzymatic activity). It is upregulated in our case LCLs.	(151–154)
IFITM3	Like GBP1 (not differentially expressed), IFITM3 was upregulated in schizophrenic brains including untreated cases (IFITM3 was upregulated in case LCLs).	(155,156)
MOXD1	This is a homolog of DBH (DBH is involved in the biosynthesis of norepinephrine from dopamine), and thus may be relevant for signal transduction. It is located within a previously reported schizophrenia linkage region at 6q23.2, and is the most upregulated transcript in our case LCLs.	(30,99–105)
NLRP1	This is a member of the Ced-4 family of apoptosis proteins, and has been demonstrated to induce apoptosis in cells when overexpressed. Nominal associations with Alzheimer's disease and with rheumatoid arthritis have been reported.	(157,158)
PRKCD	This gene is involved in the terminal translocation (when dendrite maturation begins) at the final phase of neuronal migration.	(159,160)
PTBP3	This regulator of cell differentiation binds RNA.	(136)
S100A10	This gene is thought to be involved in the regulation of cell cycle progression and differentiation. It has been implicated in major depression (decreased expression in depressed humans and in animal models), suicide (decreased expression in peripheral blood of attempters and in prefrontal cortex of suicide completers), and bipolar disorder (increased expression in peripheral blood). It was downregulated in our case LCLs.	(108–111)
SGK1	This gene participates in the regulation of neuroexcitability, inflammation, cell proliferation and apoptosis.	(161)
SYT11	A genome-wide significant for association with Parkinson's Disease has been found. A functional 33 bp repeat polymorphism in its promoter region has been reported as nominally associated with schizophrenia in a small Japanese sample. Rat hippocampus studies suggest that it contributes to the regulation of neurotransmitter release in the excitatory and inhibitory presynapses, and to postsynapse-targeted membrane trafficking in dendrites.	(112–118)
VAMP4 and STX6	These are components of a protein complex involved in vesicle–membrane fusion and important for cell adhesion. STX6 has been implicated in a GWAS of the tauopathy progressive supranuclear palsy.	(162–164)
XBP1	This transcription factor is known to be a key regulator of MHC class II genes. It has a functional promoter variant reported as nominally associated in some studies on Asian samples, but not in other studies.	(165–170)

Genes above are the highlighted (for potential relevance to schizophrenia) subset of the 89 genes differentially expressed (FDR ≤0.05) by affection status; the full list is given in Supplementary Material, Table S1.