Genetic Link Discovered for Schizophrenia in Women
A genetic variant in a gene called reelin has been identified as a significant risk factor for developing schizophrenia, but only in women. A research team led by Sagiv Shifman from the Hebrew University of Jerusalem and the University of Oxford, conducted their investigation in the Askenazi Jewish population and confirmed findings by establishing a multinational collaboration that included Irish, British, American and Chinese populations.
For schizophrenia, the age of onset, symptoms and course of the illness differ greatly between men and women. This investigation undertook a genome-wide association from pools of DNA and controls constructed separately for men and women in order to identify sex-specific effects. The research team considered 500,000 genetic variants distributed across the whole human genome in DNA from control subjects and people with schizophrenia. By comparing the genomes of the two groups the team identified one gene, only found in women, that is associated with the onset of schizophrenia.
A number of epidemiological studies have pointed to a link between heredity and schizophrenia. Until now, any attempts at identifying genes specifically associated with schizophrenia have been thwarted. Analysis of twin studies puts the likelihood of hereditability for schizophrenia at around 80 per cent.
Although reelin, which plays a part in brain development, has now been identified, it remains unclear why it is only specific to women and how the gene variant works to predispose women to schizophrenia. However, the findings give support to a neurodevelopmental origin for schizophrenia and they point to a clear sex-specific association. The research team note that sex hormones are likely to mediate changes in genetic expression. For example, the male hormone testosterone is known to decrease reelin expression in male European starlings. This could suggest a possible pathway for sex hormones.
More work is needed, but the research provides a significant boost to the study and understanding of schizophrenia. It also holds the promise of further progress in disease diagnosis and treatment, albeit in the distant future.
Shifman, S., Johannesson, M., Bronstein, M., et al (2008) Genome-Wide Association Identifies a Common Variant in the Reelin Gene that Increases the Risk of Schiphrenia Only in Women. PLoS Genet 4(2): e28. doi:10.1371/journal.pgen.0040028