Association of PIP5K2A with schizophrenia: A study in an indonesian family sample

Abstract

PIP5K2A variants have been shown to be associated with schizophrenia in Caucasian populations. This study tested 12 PIP5K2A SNPs for association with schizophrenia in a sample of 152 sib-pair families of Indonesian descent. All SNPs had previously been tested for association with schizophrenia in a German family sample by Schwab et al. [2006; Mol Psychiatry] and seven SNPs were nominally associated with schizophrenia in this previous study. The purpose of the study was to examine whether previously implicated PIP5K2A variants influence susceptibility to schizophrenia in populations of non-European descent. No single markers showed nominal association with schizophrenia in this Indonesian family sample, however multi-marker haplotypes including a previously associated exonic SNP marker revealed nominally significant association (P = 0.03). Power to detect association was greater than 80% for all previously implicated variants except for rs11013052, where power was greatly reduced due to the low minor allele frequency of this marker in the Indonesian sample. An explorative study combining the results of this study with those of our previous study indicated that rs11013052 was significantly associated with schizophrenia in the combined sample (P = 0.002). The results of this study suggest that any contribution of previously implicated DNA variants within the PIP5K2A gene to schizophrenia susceptibility in the Indonesian population is only minor.

Genetic Variations of PIP4K2A Confer Vulnerability to Poor Antipsychotic Response in Severely Ill Schizophrenia Patients

“…We failed to detect association of PIP4K2A in case-control analyses, irrespective of disease severity (data not shown). Our study further corroborated to existing evidence for involvement of PIP4K2A gene in schizophrenia disease and it was in conformity with other association studies where, major alleles of variants were found to be over-represented in disease individuals as compared to control [17], [50], [51]. Phased haplotype and diplotype are more informative and have high statistical power for an association than single SNP association because SNP do not arise independently; they have intrinsic dependency with one another due to their introduction in genealogical process [52].…”

“…Similarly, major allele ‘T’ of rs10828317 found to be associated with deficit schizophrenia and non-deficit schizophrenia patients in Dutch population [50]. Major allele ‘C’ of another intronic variant rs11013052 was found to be over-transmitted in offspring affected with schizophrenia in Indonesian population [51]. On the contrary, a three-locus haplotype C-G-A (rs10828317-rs746203-rs8341) of minor alleles was found to be associated in Chinese population [53].…”

Association Study Indicates a Protective Role of Phosphatidylinositol-4-Phosphate-5-Kinase against Tardive Dyskinesia

“…We decided to study the PIP5K2A gene, because this gene has repeatedly been shown to be associated with schizophrenia ( Schwab et al, 2006 ; Bakker et al, 2007 ; He et al, 2007 ; Saggers-Gray et al, 2008 ), and the vulnerability to develop TD is related to the likelihood to develop positive symptoms of schizophrenia. In a previous study, we have confirmed this association in the presently studied Caucasian Siberian patients with schizophrenia ( Fedorenko et al, 2013 ), but now we also demonstrated a relationship with the prevalence of TD.…”

“…PIP5K2A is involved in many different processes, including signal transduction of G-protein-coupled receptors, cell survival by protection against apoptosis, and the genetic response to oxidative stress ( Van den Bout and Divecha, 2009 ). The PIP5K2A gene has been shown to be associated with schizophrenia in several independent studies ( Schwab et al, 2006 ; Bakker et al, 2007 ; He et al, 2007 ; Saggers-Gray et al, 2008 ; Fedorenko et al, 2013 ). This is possibly related to a similar direct vs indirect pathway MSN hyperactivity explaining positive psychotic symptoms in schizophrenia as well as dyskinesia in TD.…”

Genomics, Proteomics, and the Nervous System

“…These include: 5q22-q31, where association was recently reported in the interleukin-3 (IL3) gene , which awaits replication; 10p15-q21, where evidence of association in the phophatidyl inositol-phosphate 5 kinase 2a (PIP5K2A) (Schwab et al, 2006) followed by mixed positive He et al, 2007;Saggers-Gray et al, 2008) and negative (Jamra et al, 2006) replication results; 6q21-q22, where association with the trace amine associated receptor 6 (TAAR6, previously known as TRAR4) gene located at 6q23.2 (Duan et al, 2004) has mixed positive (Pae et al, 2008;Vladimirov et al, 2007) and negative (Duan, Du et al, 2005;Ikeda et al, 2005; replications; and 15q13-q14, where evidence for linkage to an evoked potential abnormality common in patients and relatively rare in controls was supported by five additional studies reporting positive linkage evidence for schizophrenia in the same narrow region (Gejman, Sanders, Badner, Cao, & Zhang, 2001;Liu et al, 2001;Tsuang et al, 2001;Xu et al, 2001).…”