REYKJAVIK, Iceland, July 30 In a major paperpublished today in the online edition of the journal Nature, scientists fromdeCODE genetics (Nasdaq: DCGN) and the University of Iceland, along withacademic colleagues from the deCODE-led European SGENE consortium, China andthe United States, report the discovery of three rare deletions in the humangenome that confer risk of schizophrenia. Such deletions are gaps in thenormal sequence of the genome that can arise spontaneously during therecombination or reshuffling of the genome that takes place in the creation ofsperm and eggs. The deletions reported in today's study are located onchromosomes 1q21, 15q11 and 15q13, and confer, respectively, 3, 15 and 12times greater than average risk of schizophrenia. These are the first suchdeletions to be associated with risk of mental illness using large samplesizes and validated across many populations. The substantial increase in riskthey confer make them a valuable basis upon which to develop moleculardiagnostic tests to complement standard clinical diagnosis. The study, 'Largerecurrent microdeletions associated with schizophrenia,' will appear onlinetoday at www.nature.com.
"Schizophrenia is a disorder affecting thoughts and emotions. It istherefore a quintessentially human disease, but one that is little understoodbiologically and which is difficult to diagnose. These findings are importantbecause they shed light on its causes and provide a first component to amolecular test to aid in clinical diagnosis and intervention. Thesediscoveries also demonstrate one way in which we can use SNP-chips to findrarer genetic factors conferring risk of disease. In many disease areas wehave had great success of late in identifying what these chips are best suitedto find: common variants conferring relatively modest increases in risk. Butwe know that individuals with certain mental disorders such as schizophreniatend to have few children, and thus that we may have to identify a largernumber of rare but high risk variants to understand the genetic contributionto susceptibility. It is encouraging that our efforts to use SNP chips todetect rarer variations such as spontaneous deletions and duplications is nowbearing fruit," said Kari Stefansson, CEO of deCODE.
In the recent wave of discoveries of risk variants for common diseases,those associated with mental disorders such as schizophrenia, autism andothers have been conspicuously absent. This phenomenon, and the fact thatpeople with these disorders tend to have few children, suggest that rarer andperhaps spontaneously generated variants may account for a greater proportionof the disease burden in these conditions than in others. SNP-chips are notwell suited to finding rare SNPs but can, with sufficiently large samplesizes, be used to identify deletions and duplications -- known as copy numbervariations, or CNVs -- which can also be carried by healthy individuals in onegeneration and contribute to risk of disease in the next.
In order to identify novel CNVs, deCODE first analyzed the genomes of atotal of approximately 15,000 parents and offspring taking part in deCODE genediscovery programs and who had been genotyped with the more than 300,000 SNPson the HumanHap300 chip. The deCODE team discovered 66 de novo CNVs, that is,CNVs present in the genomic DNA of the offspring but not in that of theirparents. deCODE then tested these variants for association with schizophreniain more than 1,400 schizophrenics and 33,000 control subjects. The deletionson chromosomes 1q21, 15q11 and 15q13 were suggestively associated withschizophrenia in this first phase, and then validated in 3,300 cases and 8,000controls. The SGENE consortium is comprised of deCODE genetics, theNational-University Hospital in Reykjavik, the University of Aberdeen, theRavenscraig Hospital in Greenock, the Institute of Psychiatry at King'sCollege London, the National Pub