CSHL-led team discovers rare mutation dramatically increasing schizophrenia risk

Gene copy number variations of the same region, 16p11.2, are already linked to autism

An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.

The mutation in question is what scientists call a copy number variant (CNV). CNVs are areas of the genome where the number of copies of genes differs between individuals. The CNV is located in a region referred to by scientists as 16p11.2. By studying the genomes of 4,551 patients and 6,391 healthy individuals, Sebat's team has shown that having one extra copy of this region is associated with schizophrenia. The study appears online today ahead of print in the journal Nature Genetics.

The mutation identified in this study is a potent risk factor. "In the general population this duplication is quite rare, occurring in roughly one in 5,000 persons", says Sebat, "but for people that carry the extra copy, the risk of developing schizophrenia is increased by more than eight-fold". This finding is the latest in a series of studies that have pinpointed rare CNVs that confer substantial risk of schizophrenia. Others include deletions on chromosomes 1, 15 and 22.

Schizophrenia and autism: two sides of the same coin?

"This is not the first time that the 16p11.2 region has caught our eye," says Sebat. It was previously spotted in a 2007 study with Professor Michael Wigler at CSHL -- a deletion of the identical region was identified in a girl with autism. Studies by several other groups have shown that losing one copy of 16p11.2 confers high risk of autism and other developmental disorders in children.