Novel approach finds genetic clues to schizophrenia

US researchers at the Feinstein Institute for Medical Research last week reported the discovery of nine new genetic markers for schizophrenia. The study - published in the journal Proceedings of the National Academy of Sciences - used a novel whole genome scanning method to identify sections of genetic code which, when inherited together from both parents, lead to an increased risk of schizophrenia. 'If a person inherits identical copies of these markers from each parent, his or her risk for schizophrenia increases substantially', said lead author Dr Todd Lencz.

The ability to scan the whole genome for single letter changes, known as SNPs, has lead to significant advances in our understanding of the genetic basis of common diseases this year. But one of the limitations of this approach - often referred to as genome wide association studies (GWAS) - is that it cannot usually detect rare gene variants.

The alternative approach employed in this study - whole genome homozygosity association (WGHA) - gets around this problem by simultaneously looking at the genetic code from the patient's mother and father to pinpoint stretches that were inherited identically from both.

'Developing WGHA allowed us to look at patterns that emerged across clusters of SNPs, which moved us beyond our prior research', said Lencz. 'Even more importantly, the WGHA technique can now be applied to any other illnesses with a genetic component, potentially locating disease hotspots containing rare variants that might be missed with standard techniques'.

Using this method, the researchers scanned the whole genomes of 178 people with schizophrenia and 144 unaffected people. They found that 81 percent of schizophrenia patients had at least one of the nine genetic markers, compared to 45 percent of those who were unaffected. Almost half the schizophrenia patients had two or more recessive markers, compared to 11 percent of those unaffected.

Although theses findings are very promising, further research will be needed to determine the full spectrum of genes influencing an individual's risk of schizophrenia, points out Lencz. 'There's no question that the genetic architecture of schizophrenia is very complex, so we hope this will fill in one piece of the puzzle in a novel way', he said.