Table 2. Genome-wide association studies and meta-analysis in inflammatory bowel disease: summary of study designs, populations, and findings.
| Study | Population | SNPs analyzed, n | Cases/controls, n | Phenotype | Genes or loci identified |
|---|---|---|---|---|---|
| Yamazaki et al. [3] | Japanese and British Caucasian | 72,000 | 94/752* | Japanese: CD British: CD and UC | TL1A(TNFSF15) |
| Duerr et al. [4] | North American Caucasian | 304,000 | 946/977 | Ileal CD | IL23R, ATG16L1, PHOX2B, chromosome 10†, FAM92B, NCF4 |
| Hampe et al. [5] | German Caucasian | 7000‡ | 735/368 | CD | ATG16L1 |
| Libioulle et al. [2] | Belgian/French Caucasian | 302,000 | 547/928 | CD | IL23R, chromosome 5p13§ |
| Wellcome Trust Case Control Consortium [6] | British Caucasian | 469,000 | 1748/2938 | CD | IL23R, ATG16L1, chromosome 3†, chromosome 5p13§, IRGM, NKX2-3, PTPN2 |
| Franke et al. [7] | German Caucasian | 92,000 | 393/399 | CD | Chromosome 5p13§, NELL1 |
| Raelson et al. [8] | Quebec Caucasian | 164,000 | 382 trios | CD | IL23R, chromosome 17† |
| Fisher et al. [9] | British Caucasian | 10,886¶ | 905/1465** | UC | ECM1, MST1, BTNL2, HLA-DRB1 |
| Barrett et al. [10••] | North American, British, and Belgian/French populations | NA | 3230/4829 | – | IL23R, ATG16L1, IRGM, MST1, PTGER4, 5q31†, TL1A(TNFSF15), ZNF365, NKX2-3, NOD2, PTPN2, PTPN22, ITLN1, 1q24†, 1q32†, IL12B, CDKAL1, 6q21†, CCR6, 7p12†, 8q24†, 10p11†, C11orf30, LRRK2, MUC19, 13q14†, STAT3, JAK2, 21q21†, ICOSLG, ORMDL3 |
Study performed in 94 cases and 752 controls as stage 1. Findings reproduced in 490 Japanese cases and 345 controls and in 347 British IBD trios, 363 cases, and 372 controls.
A number of the studies identified association with genetic regions in which it was unclear which was the specifi c “causative” gene.
All nonsynonymous (amino acid–changing) polymorphisms.
A number of groups identified association with a variant in a gene desert on chromosome 5p13. Use of an expression database suggests that this region may be involved in regulation of the prostaglandin E receptor 4 gene (PTGER4).
Nonsynonymous and MHC tagging SNPs.
Study performed in 905 patients with UC and 1465 controls. Positive findings were tested in 936 UC cases and 1470 controls. CD—Crohn's disease; MHC—major histocompatibility complex; NA—not applicable; SNP—single nucleotide polymorphism; UC—ulcerative colitis.