Results from the first genome-wide study assessing common genetic variations in schizophrenia show that the disease is caused, at least in part, by large, rare structural changes in DNA called "copy number variants"—not the tiny, single letter alterations known as "snips" that scientists have pursued for years.
The findings support the "need for a sharp turn in the direction of schizophrenia genetics research," says David Goldstein, senior author of the study and director of the Center for Human Genome Variation at the Duke Institute for Genome Sciences & Policy.
Schizophrenia is one of the most common psychiatric disorders in the world and tends to run in families, but scientists have been unable to find any significant genetic links. Over the past two decades, dozens of possible genes and single nucleotide polymorphisms (SNPs or "snips") have been identified as possible candidates, but the current study dismisses them all.
Goldstein and lead author Anna Need, also of the Center for Human Genome Variation, worked with more than a dozen other geneticists to scan the genomes of both schizophrenia patients and healthy individuals for snips and copy number variants (CNVs). While none of the previously noted snips appeared significant in schizophrenia, several CNVs emerged as potentially causative.
Common throughout the genome but usually appearing as deletions or duplications of significant stretches of DNA, CNVs can come in a variety of sizes. However, the largest deletions—those over two million bases long—appear only in people with schizophrenia, according to Goldstein. And while CNVs have been previously implicated in schizophrenia and other psychiatric conditions, the Duke researchers are the first to argue that the apparent connection between extremely large deletions and schizophrenia suggests that CNVs are indeed pathogenic, at least in a small number of patients.
The findings were published in the open-access journal PLoS Genetics.
April 1, 2009