Researchers have discovered two new genes that increase the risk of developing inflammatory bowel disease (IBD) in childhood.

While further study is needed to identify the specific disease-causing mutations in these new genes, the researchers say the genes are particularly strong candidates to be added to the list of genes already known to affect IBD. "As we continue to find genes that interact with each other and with environmental influences in this complex, chronic disease, we are building the foundation for personalized treatments tailored to a patient's genetic profile," said co-first author Robert N Baldassano, director of the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia.

"We will resequence the gene regions we have identified to pinpoint the causative mutations in these genes," added study leader Hakon Hakonarson, director of the Center for Applied Genomics at Children's Hospital. "We strongly suspect one gene will provide a compelling target for drug development, given what's known about its biology."

Both authors direct research programmes at Children's Hospital and are also faculty members of the University of Pennsylvania School of Medicine.

Their study, performed in collaboration with researchers from the Medical College of Wisconsin, The University of Utah, Cincinnati Children's Hospital and two research hospitals in Italy, appears in advance online publication Aug. 31 in Nature Genetics.

IBD is a painful, chronic inflammation of the gastrointestinal tract, affecting about two million children and adults in the United States. Of that number, about half suffer from Crohn's disease, which can affect any part of the gastrointestinal tract, and half have ulcerative colitis, which is limited to the large intestine.

"Although the gene variants we found may have a stronger signal in pediatric IBD than in adult- onset IBD, we do not believe them to be limited to varieties of the disease that begin in childhood," said Baldassano.

The researchers performed a genome-wide association study, searching for genetic variations in DNA samples from 1,000 patients with childhood-onset IBD, compared to samples from 4,250 healthy subjects. Both patients and controls were of European ancestry.

The study team also found an association between ulcerative colitis and genes on the major histocompatiblity complex (MHC) on chromosome 6. The MHC is a large group of genes with important roles in the immune system, and this finding may help refine diagnostic techniques that would allow physicians to administer more specific therapies to their patients.

The Center for Pediatric Inflammatory Bowel Disease at Children's Hospital currently treats 1,400 children annually for IBD, and has one of the world's largest clinical research programs for IBD.

The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital.