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Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase II�� gene (PIP5K2A) with schizophrenia

Journal Article


Abstract


  • Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase II�� (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3��� untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia. �� 2006 Nature Publishing Group All rights reserved.

Publication Date


  • 2006

Citation


  • Schwab, S. G., Knapp, M., Sklar, P., Eckstein, G. N., Sewekow, C., Borrmann-Hassenbach, M., . . . Wildenauer, D. B. (2006). Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase II�� gene (PIP5K2A) with schizophrenia. Molecular Psychiatry, 11(9), 837-846. doi:10.1038/sj.mp.4001864

Scopus Eid


  • 2-s2.0-33748068453

Web Of Science Accession Number


Start Page


  • 837

End Page


  • 846

Volume


  • 11

Issue


  • 9

Place Of Publication


Abstract


  • Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase II�� (PIP5K2A), in a sample of 65 sib-pair families for which linkage had been reported. Evidence for association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic region of the gene between intron 4 and the 3��� untranslated region, a region with high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP) rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance level 0.00275) for over-transmission of the major allele coding for serine, analysed by transmission disequilibrium test using FAMHAP. Association of this SNP with schizophrenia has been also described in a sample of 273 Dutch schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in membrane transduction of neurotransmitter signals as well as in intracellular signalling, pathways that may be impaired in schizophrenia. �� 2006 Nature Publishing Group All rights reserved.

Publication Date


  • 2006

Citation


  • Schwab, S. G., Knapp, M., Sklar, P., Eckstein, G. N., Sewekow, C., Borrmann-Hassenbach, M., . . . Wildenauer, D. B. (2006). Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase II�� gene (PIP5K2A) with schizophrenia. Molecular Psychiatry, 11(9), 837-846. doi:10.1038/sj.mp.4001864

Scopus Eid


  • 2-s2.0-33748068453

Web Of Science Accession Number


Start Page


  • 837

End Page


  • 846

Volume


  • 11

Issue


  • 9

Place Of Publication