Fourth, we show that the blood levels of SAT1 (spermidine/spermine N1-acetyltransferase 1), the top biomarker identified by us, at the time of testing for this study, differentiated future as well as past hospitalizations with suicidality, in a live cohort of bipolar disorder subjects, and exhibited a similar but weaker pattern in a live cohort of psychosis (schizophrenia/schizoaffective disorder) subjects.
We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis.
In a secondary analysis, we tested gene-gene interactions between TRPM2 and iPLA2β on BD vulnerability by logistic regression using a case-only design in PLINK. iPLA2β-rs3788533 showed a borderline association with BD-I in patients with a history of psychosis in both case-control and family designs.
The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10(-8)) only for BD (P = 9.4×10(-9)) and psychosis (P = 2.0×10(-10)).
In a secondary analysis, we tested gene-gene interactions between TRPM2 and iPLA2β on BD vulnerability by logistic regression using a case-only design in PLINK. iPLA2β-rs3788533 showed a borderline association with BD-I in patients with a history of psychosis in both case-control and family designs.
Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight the possible role of altered DNA demethylation mechanisms in the pathophysiology of psychosis.
Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight the possible role of altered DNA demethylation mechanisms in the pathophysiology of psychosis.
Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis.
In the unaffected individuals (patients' relatives and healthy controls) we observed an association of KIBRA with immediate and delayed logical memory (p=0.020 and 0.025, respectively), while in patients with psychosis with delayed visual memory (p=0.05).
DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis.
It is possible that genetic variants of the NPY1R gene affect the NPY-NPY receptor type Y1 signaling system in the brain, which may result in susceptibility to methamphetamine dependence or the development of methamphetamine psychosis, but the present findings need to be confirmed on replication.
In a secondary analysis of these 6 genes among parent-proband trios with a history of psychosis, evidence of the association with SIAT4A was strengthened.
The present findings indicate that genetic variation of the GLYT1 gene may contribute to individual vulnerability to methamphetamine dependence and psychosis.
Finally, using allele specific expression analysis, we have shown that the markers associated with psychosis are also correlated with alterations in GNB1L expression, raising the hypothesis that the risk to develop psychosis at this locus could be mediated in a dose sensitive manner via gene expression.
A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis.