In the current study, the research team conducted a genome-wide association study (GWAS) to search for both common and rare genetic variants that might allow physicians to identify genetic patterns found in children with CVID but not in healthy children.
Using highly automated genotyping equipment at Children's Hospital's Center for Applied Genomics, the study team performed a GWAS in a sample of 363 patients with CVID, compared to 3,031 healthy controls. They searched for single-nucleotide polymorphisms (SNPs) as well as for rarer copy number variations (CNVs). SNPs are changes in a single base of DNA, while CNVs are deleted or repeated sequences in a stretch of DNA.
The GWAS detected a strong association with genes in the major histocompatibility complex (MHC) region, an area known to play an important role in immune-related conditions, and previously linked to CVID. The researchers also found SNPs in an area that codes for a family of proteins involved in immune responses.
In its CNV research the study team also found more than a dozen novel genes with direct or potential relevance to the immune system. The gene discoveries provided clues to the largely unknown biology of how CVID develops, shedding light on the biological mechanisms underlying the disease. "These findings provide insight into the pathogenesis of CVID and its various subtypes, and may lead to future treatments," said Orange.
The GWAS findings confirmed the genetic complexity of CVID, but more importantly for clinical application, the researchers were able to use their discoveries to develop a predictive algorithm. When they tested that algorithm on cohorts of CVID cases and controls, they were able to distinguish CVID from healthy controls with 99 percent accuracy.
|Contact: John Ascenzi|
Children's Hospital of Philadelphia