rs2188962

This case-control study in 469 Czech Crohn's disease (CD) patients and 470 controls examined the IBD5 locus, identifying two independent genetic factors: rs6596075 (OR=0.70, protective allele G, p=0.018 in dominant model) and the haplotype tagged by rs2188962 and IGR2063b_1 (OR=1.38 for IGR2063b_1, p=0.00075 in log-additive model). The study demonstrates that these two genetic factors independently contribute to CD susceptibility at the IBD5 locus.

This GWAS of pediatric IBD patients (n=94) tested associations of known IBD susceptibility loci and novel pharmacogenetic variants with response to anti-TNF α therapy. Non-response occurred in 22 patients (23%). The final predictive model combined UC diagnosis, pANCA positivity, three pharmacogenetic GWAS loci (rs975664 in TACR1 [OR 26.5], rs4855535 in FAM19A4 [OR 10.8], rs6100556 in PHACTR3 [OR 13.8]), and the known susceptibility SNP rs2836878 in BRWD1 (OR 8.0), achieving R²=0.82 and AUC=0.98. The relative risk of non-response increased 15-fold when patients carried ≥3 risk factors.

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.

This methodological study develops ProxyGeneLD software for converting genome-wide SNP association data to pathway-enriched gene sets and validates it on multiple large GWAS datasets. The authors demonstrate successful replication of pathway enrichment for plasma HDL levels (with CETP and ABCA1 in lipid metabolism pathways) across independent samples and identify positional gene clustering as a major source of spurious enrichment in pathway analyses of GWAS data.