Genetic Causes of Schizophrenia May Turn in a New Direction

The inheritable aspect of schizophrenia may be due to, in large part, structural changes in DNA called copy number variants, not more common genetic variants that have been the focus in previous studies.

The authors of the study found that, in a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenic patients, a small number of participants had CNV deletions greater than 2 Mb. Two of these, at 8p22 and 16p13.11-p12.4, were newly reported within the study.

In another group that was assessed, no deletions were found that exceeded 2 Mb. The researchers said that this suggests a “high prior probability of disease involvement when such deletions are observed in cases.”

The research was led by first author Anna Need, PhD, a postdoctoral associate in the Center for Human Genome Variation at the Duke Institute for Genome and Sciences Policy and senior author David Goldstein of the Center for Human Genome variation.

A secondary outcome of the research was evidence that supports previously reported findings on schizophrenia-associated CNVs, like the ones in NRXN1 and APBA2.

The literature also mentions what the researchers were not able to show. They did not support their hypothesis that “schizophrenic patients have a significantly greater “load” of large (>100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia.” They were also not able to show that schizophrenia-associated CNVs may inhibit genes in neurodevelopmental pathways.

The authors state that, as a whole, their research is the first study to show SNPs and CNVs in schizophrenia. Additionally, they supported the emerging hypothesis that rare, deleted variants may be more valuable in the context of genetic predisposition to schizophrenia than common polymorphisms.

“The literature is replete with dozens of genes and SNPs identified as associated with schizophrenia,” said Need. “But we systematically retested all the leading candidates and concluded that most, if not all of them, are false positives.”

For more information, click here.

specialty: psychiatry