A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

被引：226

作者：

Asano, Kouichi ^{[1
,2
,3
]}

Matsushita, Tomonaga ^{[1
,2
]}

Umeno, Junji ^{[1
,2
]}

Hosono, Naoya ^{[1
]}

Takahashi, Atsushi ^{[4
]}

Kawaguchi, Takahisa ^{[5
]}

Matsumoto, Takayuki ^{[2
]}

Matsui, Toshiyuki ^{[6
]}

Kakuta, Yoichi ^{[7
]}

Kinouchi, Yoshitaka ^{[7
]}

Shimosegawa, Tooru ^{[7
]}

Hosokawa, Masayo ^{[8
]}

Arimura, Yoshiaki ^{[8
]}

Shinomura, Yasuhisa ^{[8
]}

Kiyohara, Yutaka ^{[3
]}

Tsunoda, Tatsuhiko ^{[5
]}

Kamatani, Naoyuki ^{[4
]}

Iida, Mitsuo ^{[2
]}

Nakamura, Yusuke ^{[9
]}

Kubo, Michiaki ^{[1
,2
,3
]}

机构：

[1] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[2] Kyushu Univ, Dept Med & Clin Sci, Grad Sch Med Sci, Fukuoka 812, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Dept Environm Med, Fukuoka 812, Japan

[4] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa, Japan

[5] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Med Informat, Yokohama, Kanagawa, Japan

[6] Fukuoka Univ, Chikushi Hosp, Dept Gastroenterol, Fukuoka 81401, Japan

[7] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan

[8] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan

[9] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan

来源：

NATURE GENETICS | 2009年 / 41卷 / 12期

关键词：

INFLAMMATORY-BOWEL-DISEASE; CONGENITAL CHLORIDE DIARRHEA; COPY NUMBER VARIATION; CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; RISK-FACTORS; VARIANTS; GENE; AUTOIMMUNITY; DEFINES;

D O I：

10.1038/ng.482

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

引用

页码：1325 / U92

页数：7

共 33 条

[1] Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 diabetes, celiac disease and rheumatoid arthritis [J].

Alizadeh, Behrooz Z. ;

Valdigem, Gustavo ;

Coenen, Marieke J. H. ;

Zhernakova, Alexandra ;

Franke, Barbara ;

Monsuur, Alienke ;

van Riel, Piet L. C. M. ;

Barrera, Pilar ;

Radstake, Timothy R. D. J. ;

Roep, Bart O. ;

Wijmenga, Cisca ;

Koeleman, Bobby P. C. .

HUMAN MOLECULAR GENETICS, 2007, 16 (21) :2552-2559

[2] Investigation of Crohn's Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship [J].

Anderson, Carl A. ;

Massey, Dunecan C. O. ;

Barrett, Jeffrey C. ;

Prescott, Natalie J. ;

Tremelling, Mark ;

Fisher, Sheila A. ;

Gwilliam, Rhian ;

Jacob, Jemima ;

Nimmo, Elaine R. ;

Drummond, Hazel ;

Lees, Charlie W. ;

Onnie, Clive M. ;

Hanson, Catherine ;

Blaszczyk, Katarzyna ;

Ravindrarajah, Radhi ;

Hunt, Sarah ;

Varma, Dhiraj ;

Hammond, Naomi ;

Lewis, Gregory ;

Attlesey, Heather ;

Watkins, Nick ;

Ouwehand, Willem ;

Strachan, David ;

McArdle, Wendy ;

Lewis, Cathryn M. ;

Lobo, Alan ;

Sanderson, Jeremy ;

Jewell, Derek P. ;

Deloukas, Panos ;

Mansfield, John C. ;

Mathew, Christopher G. ;

Satsangi, Jack ;

Parkes, Miles .

GASTROENTEROLOGY, 2009, 136 (02) :523-529

[3] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[4] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[5] Induction of macrophage secretion of tumor necrosis factor a through Fcγ receptor IIa engagement by rheumatoid arthritis-specific autoantibodies to citrullinated proteins complexed with fibrinogen [J].

Clavel, Cyril ;

Nogueira, Leonor ;

Laurent, Laetitia ;

Lobagiu, Cristina ;

Vincent, Christian ;

Sebbag, Mireille ;

Serre, Guy .

ARTHRITIS AND RHEUMATISM, 2008, 58 (03) :678-688

[6] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[7] A genome-wide association study identifies IL23R as an inflammatory bowel disease gene [J].

Duerr, Richard H. ;

Taylor, Kent D. ;

Brant, Steven R. ;

Rioux, John D. ;

Silverberg, Mark S. ;

Daly, Mark J. ;

Steinhart, A. Hillary ;

Abraham, Clara ;

Regueiro, Miguel ;

Griffiths, Anne ;

Dassopoulos, Themistocles ;

Bitton, Alain ;

Yang, Huiying ;

Targan, Stephan ;

Datta, Lisa Wu ;

Kistner, Emily O. ;

Schumm, L. Philip ;

Lee, Annette T. ;

Gregersen, Peter K. ;

Barmada, M. Michael ;

Rotter, Jerome I. ;

Nicolae, Dan L. ;

Cho, Judy H. .

SCIENCE, 2006, 314 (5804) :1461-1463

[8] FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity [J].

Fanciulli, Manuela ;

Norsworthy, Penny J. ;

Petretto, Enrico ;

Dong, Rong ;

Harper, Lorraine ;

Kamesh, Lavanya ;

Heward, Joanne M. ;

Gough, Stephen C. L. ;

de Smith, Adam ;

Blakemore, Alexandra I. F. ;

Owen, Catherine J. ;

Pearce, Simon H. S. ;

Teixeira, Luis ;

Guillevin, Loic ;

Graham, Deborah S. Cunninghame ;

Pusey, Charles D. ;

Cook, H. Terence ;

Vyse, Timothy J. ;

Aitman, Timothy J. .

NATURE GENETICS, 2007, 39 (06) :721-723

[9] Ulcerative colitis [J].

Ungaro, Ryan ;

Mehandru, Saurabh ;

Allen, Patrick B. ;

Peyrin-Biroulet, Laurent ;

Colombel, Jean-Frederic .

LANCET, 2017, 389 (10080) :1756-1770

[10] Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility [J].

Franke, Andre ;

Balschun, Tobias ;

Karlsen, Tom H. ;

Sventoraityte, Jurgita ;

Nikolaus, Susanna ;

Mayr, Gabriele ;

Domingues, Francisco S. ;

Albrecht, Mario ;

Nothnagel, Michael ;

Ellinghaus, David ;

Sina, Christian ;

Onnie, Clive M. ;

Weersma, Rinse K. ;

Stokkers, Pieter C. F. ;

Wijmenga, Cisca ;

Gazouli, Maria ;

Strachan, David ;

McArdle, Wendy L. ;

Vermeire, Severine ;

Rutgeerts, Paul ;

Rosenstiel, Philip ;

Krawczak, Michael ;

Vatn, Morten H. ;

Mathew, Christopher G. ;

Schreiber, Stefan .

NATURE GENETICS, 2008, 40 (11) :1319-1323

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