Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish...

Area of Science:

• Genetics
• Gastroenterology
• Immunology

Background:

• Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex disorders influenced by common genetic variants.
• Understanding the genetic architecture of IBD across different age groups and populations is crucial for developing targeted therapies.

Purpose of the Study:

• To define the genetic architecture of pediatric and adult-onset IBD in the Polish population.
• To identify shared and unique genetic factors contributing to early-onset versus adult-onset IBD.
• To investigate the role of rare variants in early-onset IBD through whole exome sequencing.

Main Methods:

• Genome-wide association study (GWAS) using pooled DNA, followed by individual genotyping validation.
• Whole exome sequencing (WES) on early-onset and late-onset IBD patients and healthy controls.
• Recruitment of 1495 IBD patients (CD and UC, pediatric and adult) and 934 healthy controls from Poland.

Main Results:

• 31 single nucleotide polymorphisms (SNPs) were replicated for association with IBD.
• A novel association with BRD2 (rs1049526) showed high significance (P=5.2×10⁻¹¹, OR=2.43).
• Whole exome sequencing identified numerous rare, potentially deleterious variants in IBD and innate immunity genes, with over-representation in affected children.

Conclusions:

• Significant differences exist in the polygenic architecture of pediatric- versus adult-onset IBD.
• A higher burden of rare and deleterious variants in pediatric IBD suggests contributions from unexplained genetic components.
• Genetic findings highlight population-specific and age-specific factors influencing IBD development.