Genetic association study in schizophrenia and intermediate phenotypes

Familiy, twin and adoption studies show a clear heritability of schizophrenia. Therefore we recruited a large case-control- and family-based study. 700 patients with schizophrenia according to DSM-IV and 200 first degree relatives were included. Furthermore, 2000 community-based healthy volunteers without relevant somatic, and with no history of psychiatric disorders in themselves and in first-degree relatives entered the study. All subjects are screened by SCID and characterized by other specific instruments. Genotyping of candidate genes has been performed using MALDI-TOF. Single nucleotide polymorphisms (SNPs) were selected (tag SNPs in addition to common functional variants and published candidate SNPs localized in selected genes). Furthermore, we use endophenotypes as a complementary approach. Our ongoing endophenotype project includes a broad range of schizophrenia endophenotypes. These comprise, among others, neuropsychological (e.g. working memory, attention/vigilance, verbal/visual learning and memory, speed of processing, and problem solving) measurements. We performed full scale IQ measurements in over 2000 healthy subjects, schizophrenic patients and their first degree relatives. Furthermore, we assessed the other above-mentioned endophenotypes in over 700 subjects. We present here data on the influence of common genetic variations on individual differences on cognitive performance and schizophrenia.

This study was supported by GSK