Project 2

Phophatidylinositol-4-phosphate-5-kinase gene (PIP5K2A) variants and association with schizophrenia

Background

Schizophrenia is a devastating mental disorder affecting approximately 1% of the population worldwide. Evidence for participation of genetic factors has been obtained by family-, twin-, and adoption studies.

Our goal is the identification and characterization of genes conferring risk to schizophrenia. Knowledge of the genes and the gene defect will aid in elucidation of the pathophysiology underlying development of schizophrenia.

Association of schizophrenia with DNA sequence variants in Phosphatidylinositol-4-phosphate 5 kinase has been detected in a sample of families with schizophrenia by our group.

Aims and experimental design

The aim of the current project will be to test additional family samples for association of variants in the PIPK2A gene with schizophrenia.

A sample of 152 families from Indonesia (686 family members) with at least two affected offspring and a sample of 171 families from Germany (703 family members) with extensive neuropsychiological characterization are available. We plan to genotype 10 SNPs in these family samples. This would be necessary to deal with the possibility of allelic heterogeneity, where we would expect in different samples different SNPs in LD with the illness.

Significance

Studying genetic variation is an important first step for the identification of susceptibility genes contributing to the development of schizophrenia. Identification of the molecular causes of schizophrenia would provide new targets for the development of novel pharmacological treatments.