rs8049439

This PhD thesis by Paul Henderson comprises multiple studies on paediatric inflammatory bowel disease (PIBD) in Scotland, including epidemiological studies documenting a 76% rise in IBD incidence, genetic association studies identifying ICOSLG SNP rs8126734-A as overtransmitted in IBD/CD (p=0.0467, OR 1.85 for CD; p=0.0084), CRP gene variants rs1130864-A and rs1417938-A associated with PIBD susceptibility (OR 1.56-1.89 for CD), and functional characterization of NOD2 and autophagy pathways in Crohn's disease pathogenesis.

This PhD thesis encompasses multiple studies on pediatric inflammatory bowel disease (IBD): epidemiological analysis shows rising incidence in Scotland (4.45 to 7.82 per 100,000 per year); transmission disequilibrium testing identified rs8126734-A as overtransmitted in IBD and CD (OR 1.48, p=0.047; OR 1.85 for CD, p=0.008); genome-wide association meta-analysis confirmed strong signals in ICOSLG 3'UTR for CD susceptibility; CRP gene variants (rs1417938, rs1130864) showed significant overtransmission (p=0.006, p=0.015); and faecal calprotectin demonstrated superior diagnostic accuracy for PIBD detection (sensitivity 0.93, specificity 0.74).

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.

This case-control study of 563 Canadian children with pediatric-onset Crohn's disease and 553 controls confirmed associations between SNPs at two novel pediatric-specific loci (rs1250550 at 10q22.3, p=0.026; rs8049439 at 16p11.2, p=0.04) and disease susceptibility. Additionally, 6 of 16 previously reported adult CD loci were significantly associated with pediatric CD, demonstrating substantial genetic overlap between disease forms.