CNV Study Reveals New Targets for Multiple Diseases

A study published today in Nature Communications discovered how relatively rare—albeit recurrent—genetic variations can influence a variety of common diseases from autoimmune diseases to neuropsychological diseases to cancer. With the genetic underpinnings of these conditions known, existing drugs could potentially be repurposed to target them.

Certain genomic regions are repeated, and the number of repeats varies from individual to individual. This is called “copy number variation (CNV).” Rare CNVs are events that often predispose people to medical conditions, whereas more common CNVs are usually well tolerated.

“This analysis provides us with a dense map of the impact of rare recurrent copy number variations, which represent an important source of genetic variation in our genome, often predisposing us to, and sometimes causing, complex diseases,” says senior author Hakon Hakonarson of the Children’s Hospital of Philadelphia. “Our study showed that previous methods are likely not capturing the accurate incidence or prevalence of rare copy number variation regions that directly impact human health.”

The team genotyped 100,028 individuals from populations of European ancestry using either genome-wide SNP arrays or array comparative genomic hybridization platforms. More than 99% of the CNV regions uncovered, while individually rare, were recurrent, meaning that they occurred in at least two individuals.

Among these regions that are most clinically relevant are those with homozygous deletions. The team identified 375 previously unreported regions like this. In addition to confirming disease-associated CNV regions from previous studies, the researchers discovered several previously unreported regions that match genes that are already of clinical interest, in some cases because drugs that target relevant pathways may already exist.

“The number of gene candidates found in our study that warrant further studies establishes the strong correlation between regions of copy number variations and what we already know about the genome,” Hakonarson says. “While ongoing, large-scale studies focusing on new discoveries are important, we believe that further investigating these newly identified regions in parallel will continue to yield even more clinically relevant information and accelerate precision medicine.”