Common variants at five new loci associated with early-onset inflammatory bowel disease.
Imielinski M., Baldassano RN., Griffiths A., Russell RK., Annese V., Dubinsky M., Kugathasan S., Bradfield JP., Walters TD., Sleiman P., Kim CE., Muise A., Wang K., Glessner JT., Saeed S., Zhang H., Frackelton EC., Hou C., Flory JH., Otieno G., Chiavacci RM., Grundmeier R., Castro M., Latiano A., Dallapiccola B., Stempak J., Abrams DJ., Taylor K., McGovern D., Western Regional Alliance for Pediatric IBD None., Silber G., Wrobel I., Quiros A., International IBD Genetics Consortium None., Barrett JC., Hansoul S., Nicolae DL., Cho JH., Duerr RH., Rioux JD., Brant SR., Silverberg MS., Taylor KD., Barmuda MM., Bitton A., Dassopoulos T., Datta LW., Green T., Griffiths AM., Kistner EO., Murtha MT., Regueiro MD., Rotter JI., Schumm LP., Steinhart AH., Targan SR., Xavier RJ., NIDDK IBD Genetics Consortium None., Libioulle C., Sandor C., Lathrop M., Belaiche J., Dewit O., Gut I., Heath S., Laukens D., Mni M., Rutgeerts P., Van Gossum A., Zelenika D., Franchimont D., Hugot JP., de Vos M., Vermeire S., Louis E., Belgian-French IBD Consortium None., Wellcome Trust Case Control Consortium None., Cardon LR., Anderson CA., Drummond H., Nimmo E., Ahmad T., Prescott NJ., Onnie CM., Fisher SA., Marchini J., Ghori J., Bumpstead S., Gwillam R., Tremelling M., Delukas P., Mansfield J., Jewell D., Satsangi J., Mathew CG., Parkes M., Georges M., Daly MJ., Heyman MB., Ferry GD., Kirschner B., Lee J., Essers J., Grand R., Stephens M., Levine A., Piccoli D., Van Limbergen J., Cucchiara S., Monos DS., Guthery SL., Denson L., Wilson DC., Grant SFA., Daly M., Silverberg MS., Satsangi J., Hakonarson H.
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.