Genetics of Schizophrenia

The Neuropsychiatric Genetics Laboratory at WAIMR aims at identification and characterisation of genes and their encoded proteins conferring risk to:

1. schizophrenia
2. addiction (heroin, alcohol, nicotine)
3. depression in Parkinson's Disease

We apply molecular genetic methods like linkage-, and association analysis, we study evaluation of gene- and protein expression as well as conduct functional studies of proteins potentially involved in development of these disorders.

The laboratory is jointly operated by Associate Professor Sibylle Schwab, Laboratory Head WAIMR and Professor Dieter Wildenauer, Deputy Director of the Clinical Centre for Research in Neuropsychiatry.

Senior Research Staff

A/Professor Sybille Schwab Head, Genetics of Schizophrenia Research: genetics of schizophrenia; DNA variants associated with schizophrenia

Research Details

We have sampls of families as well as of patients available for molecular genetic studies. These samples have been collected during the last 20 years in collaboration with clinical groups in Germany, Israel, Hungary (schizophrenia: 82 sib-pair families, 152 patient/parents families) Indonesia (schizophrenia: 152 sib-pair families), and Western Australia (47 Parkinson patients, heroin dependent individuals currently collected). We participate with some of these samples in international collaborative projects.

• Currently, we are studying candidate genes and their encoded proteins involved in:
  • Cell Signalling Pathways: We have been able to show association of schizophrenia with DNA sequence variants for AKT/protein kinase B and for phosphatidylinositol-4-phosphate 5-kinase II-alpha (PIP5K2A). Current work includes: replication studies in additional samples, identification of variants with impact on function, investigation of impaired function, association studies with other genes involved in the respective pathways.
  • Neurotransmission: Association of schizophrenia with DNA sequence variants in the gene for DTNBP1, a gene located in chromosome 6p, has been detected in our family samples with linkage for this region. We aim at identification of variants directly involved in the enhanced risk for development of schizophrenia employing sequencing and large scale SNP genotyping. Other genes involved in neurotransmission including mainly glutamate- and GABA receptor genes are studied for association with schizophrenia in our samples.
  • Neurodevelopment: Association of DNA sequence variants in the gene for neuregulin in one of our family samples suggested involvement of genes in neurodevelopmental pathways. Currently we are testing in our samples DNA sequence polymorphisms in genes Erb, Olig2, Disc1, where evidence for association has been reported.
• A genome wide scan for genetic linkage in 152 Indonesian families using a panel of 402 microsatellite markers suggested evidence for linkage on chromosome 3p, 1q, and 5q. We are planning association studies using a candidate gene approach as well as large scale SNP genotyping for identification of genetic risk factors. Colleagues at the University of Indonesia are currently collecting an additional sample of 2000 individuals for replication studies.
• A sample of approximately thousand heroin addicts is currently being collected in collaboration with Professor G Hulse, UWA. This sample will be used to study association of DNA sequence variants in genes involved in rewarding pathways and metabolism. In addition we plan to correlate these DNA sequence variants with treatment response (pharmacogenetic studies).
• In collaboration with Professor S Starkstein, UWA, we are conducting a study on genetic susceptibility for depression in Parkinson's disease.

International Collaborations

We have contributed 102 families with schizophrenia to an international collaboration comprising 900 families in total from 8 participating sites. A SNP genome-wide scan has been performed and detected linkage with schizophrenia on chromosome 2q, 8p and 9q. A large scale SNP- and CNV association study is in the planning stage (NIH funded).

We collaborate with Professor K Kendler, VCU, Richmond, VA, USA and Professor K Kidd, Yale, USA to investigate differences in allelic association of the potential schizophrenia susceptibility gene dysbindin (NIH funded).

Major Highlights / Achievements

1995	First replication of linkage in schizophrenia on chromosome 6p, together with K Kendler, R Straub
2000	Genome-wide linkage study in 71 sib-pair families with schizophrenia from Germany and Israel suggests linkage to chromosome 6p, 10p, 5q, (Schwab et al, 2000, Mol Psychiatry 5:638-649)
2003	First replication of association of DNA sequence variants in the gene for dysbindin, in the region with linkage on chromosome 6p
2006	Identification of association of an exonic DNA sequence variant in the gene for PIP5K2A located in the linked region of chromosome 10p (Schwab et al, 2006, Mol Psychiatry 11:837-846)
2007	Genome-wide scan in 152 sib-pair families with schizophrenia from Indonesia detects evidence for linkage on chromosome 3p (in preparation)