{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:06:39Z","timestamp":1790496399016,"version":"4.1.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Genomic Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ankylosing spondylitis (AS) is a common chronic immune-mediated arthropathy affecting primarily the spine and pelvis. The condition is strongly associated with <jats:italic>HLA-B*27<\/jats:italic> as well as other human leukocyte antigen variants and at least 47 individual non-MHC-associated variants. However, substantial additional heritability remains as yet unexplained. To identify further genetic variants associated with the disease, we undertook an association study of AS in 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. A novel association achieving genome-wide significance was noted at <jats:italic>CDKAL1<\/jats:italic>. Suggestive associations were demonstrated with common variants in <jats:italic>FAM118A<\/jats:italic>, <jats:italic>C7orf72<\/jats:italic> and <jats:italic>FAM114A1<\/jats:italic> and with a low-frequency variant in <jats:italic>PNPLA1.<\/jats:italic> Two of the variants have been previously associated with inflammatory bowel disease (IBD; <jats:italic>CDKAL1<\/jats:italic> and <jats:italic>C7orf72<\/jats:italic>). These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having similar aetiopathogenesis.<\/jats:p>","DOI":"10.1038\/npjgenmed.2016.8","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T13:49:43Z","timestamp":1462369783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease"],"prefix":"10.1038","volume":"1","author":[{"given":"Philip C","family":"Robinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Leo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J","family":"Pointon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Cremin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A","family":"Bradbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Stebbings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Australian Osteoporosis Genetics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"McCloskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Eisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Sambrook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Prince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Dennison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Wellcome Trust Case Control Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Management Committee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenefer M","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Bramon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P","family":"Casas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden","family":"Corvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Deloukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Duncanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Jankowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh S","family":"Markus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin NA","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Plomin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rautanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Sawcer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C","family":"Trembath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananth C","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Data and Analysis Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris C A","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Band","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Bellenguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Hellenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Giannoulatou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Pirinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Strange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damjan","family":"Vukcevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"DNA, Genotyping, Data QC and Informatics Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordelia","family":"Langford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Edkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhian","family":"Gwilliam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Blackburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzannah J","family":"Bumpstead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Dronov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gillman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alagurevathi","family":"Jayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen T","family":"McCann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Liddle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C","family":"Potter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhi","family":"Ravindrarajah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Ricketts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Waller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Weston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Widaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Whittaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Deloukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Publications Committee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenefer M","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden","family":"Corvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris CA","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B","family":"Wordsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,4]]},"reference":[{"key":"BFnpjgenmed20168_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.molimm.2013.06.013","volume":"57","author":"PC Robinson","year":"2014","unstructured":"Robinson, P. C. & Brown, M. A. Genetics of ankylosing spondylitis. Mol. Immunol. 57, 2\u201311 (2014).","journal-title":"Mol. Immunol."},{"key":"BFnpjgenmed20168_CR2","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/S0140-6736(13)61134-4","volume":"382","author":"D Baeten","year":"2013","unstructured":"Baeten, D. et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382, 1705\u20131713 (2013).","journal-title":"Lancet"},{"key":"BFnpjgenmed20168_CR3","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1038\/ng.2007.17","volume":"39","author":"PR Burton","year":"2007","unstructured":"Burton, P. R. et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 39, 1329\u20131337 (2007).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR4","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/ng.873","volume":"43","author":"DM Evans","year":"2011","unstructured":"Evans, D. M. et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat. Genet. 43, 761\u2013767 (2011).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR5","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/ng.513","volume":"42","author":"JD Reveille","year":"2010","unstructured":"Reveille, J. D. et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat. Genet. 42, 123\u2013127 (2010).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR6","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/242121a0","volume":"242","author":"MF Caffrey","year":"1973","unstructured":"Caffrey, M. F. & James, D. C. Human lymphocyte antigen association in ankylosing spondylitis. Nature 242, 121 (1973).","journal-title":"Nature"},{"key":"BFnpjgenmed20168_CR7","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/S0140-6736(73)91360-3","volume":"1","author":"DA Brewerton","year":"1973","unstructured":"Brewerton, D. A. et al. Ankylosing spondylitis and HL-A 27. Lancet 1, 904\u2013907 (1973).","journal-title":"Lancet"},{"key":"BFnpjgenmed20168_CR8","doi-asserted-by":"publisher","first-page":"e1001195","DOI":"10.1371\/journal.pgen.1001195","volume":"6","author":"P Danoy","year":"2010","unstructured":"Danoy, P. et al. Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease. PLoS Genet. 6, e1001195 (2010).","journal-title":"PLoS Genet."},{"key":"BFnpjgenmed20168_CR9","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1056\/NEJM197304052881403","volume":"288","author":"L Schlosstein","year":"1973","unstructured":"Schlosstein, L., Terasaki, P. I., Bluestone, R. & Pearson, C. M. High association of an HL-A antigen, W27, with ankylosing spondylitis. N. Engl. J. Med. 288, 704\u2013706 (1973).","journal-title":"N. Engl. J. Med."},{"key":"BFnpjgenmed20168_CR10","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1136\/annrheumdis-2015-207416","volume":"74","author":"PC Robinson","year":"2015","unstructured":"Robinson, P. C. et al. ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients. Ann. Rheum. Dis. 74, 1627\u20131629 (2015).","journal-title":"Ann. Rheum. Dis."},{"key":"BFnpjgenmed20168_CR11","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/ng.2667","volume":"45","author":"A Cortes","year":"2013","unstructured":"Cortes, A. et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat. Genet. 45, 730\u2013738 (2013).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR12","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/nature09534","volume":"467","author":"Genomes Project, C.","year":"2010","unstructured":"Genomes Project, C. et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061\u20131073 (2010).","journal-title":"Nature"},{"key":"BFnpjgenmed20168_CR13","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nrg2344","volume":"9","author":"MI McCarthy","year":"2008","unstructured":"McCarthy, M. I. et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 9, 356\u2013369 (2008).","journal-title":"Nat. Rev. Genet."},{"key":"BFnpjgenmed20168_CR14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1126\/science.1219240","volume":"337","author":"JA Tennessen","year":"2012","unstructured":"Tennessen, J. A. et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337, 64\u201369 (2012).","journal-title":"Science"},{"key":"BFnpjgenmed20168_CR15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature11690","volume":"493","author":"W Fu","year":"2013","unstructured":"Fu, W. et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 493, 216\u2013220 (2013).","journal-title":"Nature"},{"key":"BFnpjgenmed20168_CR16","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1086\/513473","volume":"80","author":"GV Kryukov","year":"2007","unstructured":"Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80, 727\u2013739 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnpjgenmed20168_CR17","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/ng.717","volume":"42","author":"A Franke","year":"2010","unstructured":"Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42, 1118\u20131125 (2010).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR18","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1038\/ng.175","volume":"40","author":"JC Barrett","year":"2008","unstructured":"Barrett, J. C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40, 955\u2013962 (2008).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1136\/jmg.2007.053595","volume":"45","author":"N Wolf","year":"2008","unstructured":"Wolf, N. et al. Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease. J. Med. Genet. 45, 114\u2013116 (2008).","journal-title":"J. Med. Genet."},{"key":"BFnpjgenmed20168_CR20","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1053\/j.gastro.2008.10.032","volume":"136","author":"CA Anderson","year":"2009","unstructured":"Anderson, C. A. et al. Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology 136, 523\u2013529, e3 (2009).","journal-title":"Gastroenterology"},{"key":"BFnpjgenmed20168_CR21","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1126\/science.1142364","volume":"316","author":"E Zeggini","year":"2007","unstructured":"Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336\u20131341 (2007).","journal-title":"Science"},{"key":"BFnpjgenmed20168_CR22","doi-asserted-by":"publisher","first-page":"e1000608","DOI":"10.1371\/journal.pgen.1000608","volume":"5","author":"T Kwan","year":"2009","unstructured":"Kwan, T. et al. Tissue effect on genetic control of transcript isoform variation. PLoS Genet. 5, e1000608 (2009).","journal-title":"PLoS Genet."},{"key":"BFnpjgenmed20168_CR23","doi-asserted-by":"publisher","first-page":"e17160","DOI":"10.1371\/journal.pone.0017160","volume":"6","author":"P Di Meglio","year":"2011","unstructured":"Di Meglio, P. et al. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS ONE 6, e17160 (2011).","journal-title":"PLoS ONE"},{"key":"BFnpjgenmed20168_CR24","doi-asserted-by":"publisher","first-page":"9560","DOI":"10.1073\/pnas.1017854108","volume":"108","author":"R Sarin","year":"2011","unstructured":"Sarin, R., Wu, X. & Abraham, C. Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proc. Natl Acad. Sci. USA 108, 9560\u20139565 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnpjgenmed20168_CR25","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.humimm.2012.01.015","volume":"73","author":"AR Morgan","year":"2012","unstructured":"Morgan, A. R., Lam, W. J., Han, D. Y., Fraser, A. G. & Ferguson, L. R. Genetic variation within TLR10 is associated with Crohn's disease in a New Zealand population. Hum. Immunol. 73, 416\u2013420 (2012).","journal-title":"Hum. Immunol."},{"key":"BFnpjgenmed20168_CR26","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/gene.2011.41","volume":"12","author":"C Abad","year":"2011","unstructured":"Abad, C. et al. Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2. Genes Immun. 12, 635\u2013642 (2011).","journal-title":"Genes Immun."},{"key":"BFnpjgenmed20168_CR27","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S0889-857X(05)70042-9","volume":"24","author":"F De Keyser","year":"1998","unstructured":"De Keyser, F. et al. Bowel inflammation and the spondyloarthropathies. Rheum. Dis. Clin. North Am. 24, 785\u2013813, ix-x (1998).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"BFnpjgenmed20168_CR28","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/0016-5085(89)91557-6","volume":"96","author":"M De Vos","year":"1989","unstructured":"De Vos, M. et al. Ileocolonoscopy in seronegative spondylarthropathy. Gastroenterology 96, 339\u2013344 (1989).","journal-title":"Gastroenterology"},{"key":"BFnpjgenmed20168_CR29","first-page":"294","volume":"12","author":"H Mielants","year":"1985","unstructured":"Mielants, H., Veys, E. M., Cuvelier, C., De Vos, M. & Botelberghe, L. HLA-B27 related arthritis and bowel inflammation. Part 2. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J. Rheumatol. 12, 294\u2013298 (1985).","journal-title":"J. Rheumatol."},{"key":"BFnpjgenmed20168_CR30","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1002\/art.22812","volume":"56","author":"B Thjodleifsson","year":"2007","unstructured":"Thjodleifsson, B., Geirsson, A. J., Bjornsson, S. & Bjarnason, I. A common genetic background for inflammatory bowel disease and ankylosing spondylitis: a genealogic study in Iceland. Arthritis Rheumatol. 56, 2633\u20132639 (2007).","journal-title":"Arthritis Rheumatol."},{"key":"BFnpjgenmed20168_CR31","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1002\/art.38097","volume":"65","author":"T Frisell","year":"2013","unstructured":"Frisell, T. et al. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor\/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheumatol. 65, 2773\u20132782 (2013).","journal-title":"Arthritis Rheumatol."},{"key":"BFnpjgenmed20168_CR32","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrg3502","volume":"14","author":"M Parkes","year":"2013","unstructured":"Parkes, M., Cortes, A., van Heel, D. A. & Brown, M. A. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat. Rev. Genet. 14, 661\u2013673 (2013).","journal-title":"Nat. Rev. Genet."},{"key":"BFnpjgenmed20168_CR33","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.rdc.2012.08.018","volume":"38","author":"PC Robinson","year":"2012","unstructured":"Robinson, P. C. & Brown, M. A. The genetics of ankylosing spondylitis and axial spondyloarthritis. Rheum. Dis. Clin. North Am. 38, 539\u2013553 (2012).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"BFnpjgenmed20168_CR34","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/j.1471-4159.2006.04093.x","volume":"99","author":"M Boucquey","year":"2006","unstructured":"Boucquey, M. et al. Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in teratocarcinoma-derived neuroectodermic precursor cells. J. Neurochem. 99, 657\u2013669 (2006).","journal-title":"J. Neurochem."},{"key":"BFnpjgenmed20168_CR35","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1073\/pnas.1324266111","volume":"111","author":"SM Lee","year":"2014","unstructured":"Lee, S. M. et al. Toll-like receptor 10 is involved in induction of innate immune responses to influenza virus infection. Proc. Natl Acad Sci. USA 111, 3793\u20133798 (2014).","journal-title":"Proc. Natl Acad Sci. USA"},{"key":"BFnpjgenmed20168_CR36","doi-asserted-by":"publisher","first-page":"265","DOI":"10.2217\/ijr.12.84","volume":"8","author":"TJ Kenna","year":"2013","unstructured":"Kenna, T. J. & Brown, M. Immunopathogenesis of ankylosing spondylitis. Int. J. Clin. Rheumatol. 8, 265\u2013274 (2013).","journal-title":"Int. J. Clin. Rheumatol."},{"key":"BFnpjgenmed20168_CR37","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248\u2013249 (2010).","journal-title":"Nat. Methods"},{"key":"BFnpjgenmed20168_CR38","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/ng.1056","volume":"44","author":"A Grall","year":"2012","unstructured":"Grall, A. et al. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat. Genet. 44, 140\u2013147 (2012).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR39","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/ng.3390","volume":"47","author":"J Yang","year":"2015","unstructured":"Yang, J. et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47, 1114\u20131120 (2015).","journal-title":"Nat. Genet."},{"key":"BFnpjgenmed20168_CR40","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1002\/art.38967","volume":"67","author":"ME Costello","year":"2015","unstructured":"Costello, M. E. et al. Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol. 67, 686\u2013691 (2015).","journal-title":"Arthritis Rheumatol."},{"key":"BFnpjgenmed20168_CR41","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/ar4228","volume":"15","author":"M-E Costello","year":"2013","unstructured":"Costello, M.-E., Elewaut, D., Kenna, T. & Brown, M. A. Microbes, the Gut and Ankylosing Spondylitis. Arthritis Res. Ther. 15, 214 (2013).","journal-title":"Arthritis Res. Ther."},{"key":"BFnpjgenmed20168_CR42","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1002\/art.38873","volume":"67","author":"PC Robinson","year":"2015","unstructured":"Robinson, P. C. et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol. 67, 140\u2013151 (2015).","journal-title":"Arthritis Rheumatol."},{"key":"BFnpjgenmed20168_CR43","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/art.1780270401","volume":"27","author":"S van der Linden","year":"1984","unstructured":"van der Linden, S., Valkenburg, H. A. & Cats, A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheumatol. 27, 361\u2013368 (1984).","journal-title":"Arthritis Rheumatol."},{"key":"BFnpjgenmed20168_CR44","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1093\/bioinformatics\/bts479","volume":"28","author":"JI Goldstein","year":"2012","unstructured":"Goldstein, J. I. et al. zCall: a rare variant caller for array-based genotyping: genetics and population analysis. Bioinformatics 28, 2543\u20132545 (2012).","journal-title":"Bioinformatics"},{"key":"BFnpjgenmed20168_CR45","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.ajhg.2014.01.009","volume":"94","author":"GM Peloso","year":"2014","unstructured":"Peloso, G. M. et al. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks. Am. J. Hum. Genet. 94, 223\u2013232 (2014).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnpjgenmed20168_CR46","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","volume":"89","author":"MC Wu","year":"2011","unstructured":"Wu, M. C. et al. Rare-variant association testing for sequencing data with the sequence kernel association test. Am. J. Hum. Genet. 89, 82\u201393 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnpjgenmed20168_CR47","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.ajhg.2010.04.005","volume":"86","author":"AL Price","year":"2010","unstructured":"Price, A. L. et al. Pooled association tests for rare variants in exon-resequencing studies. Am. J. Hum. Genet. 86, 832\u2013838 (2010).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnpjgenmed20168_CR48","doi-asserted-by":"publisher","first-page":"e1000384","DOI":"10.1371\/journal.pgen.1000384","volume":"5","author":"BE Madsen","year":"2009","unstructured":"Madsen, B. E. & Browning, S. R. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 5, e1000384 (2009).","journal-title":"PLoS Genet."},{"key":"BFnpjgenmed20168_CR49","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/gepi.20450","volume":"34","author":"AP Morris","year":"2010","unstructured":"Morris, A. P. & Zeggini, E. An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet. Epidemiol. 34, 188\u2013193 (2010).","journal-title":"Genet. Epidemiol."},{"key":"BFnpjgenmed20168_CR50","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ajhg.2008.06.024","volume":"83","author":"B Li","year":"2008","unstructured":"Li, B. & Leal, S. M. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am. J. Hum. Genet. 83, 311\u2013321 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnpjgenmed20168_CR51","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/biostatistics\/kxs014","volume":"13","author":"S Lee","year":"2012","unstructured":"Lee, S., Wu, M. C. & Lin, X. Optimal tests for rare variant effects in sequencing association studies. Biostatistics 13, 762\u2013775 (2012).","journal-title":"Biostatistics"}],"container-title":["npj Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/npjgenmed20168.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/npjgenmed20168","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/npjgenmed20168.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:25:18Z","timestamp":1672835118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/npjgenmed20168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,4]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,11,30]]}},"alternative-id":["BFnpjgenmed20168"],"URL":"https:\/\/doi.org\/10.1038\/npjgenmed.2016.8","relation":{},"ISSN":["2056-7944"],"issn-type":[{"value":"2056-7944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,4]]},"assertion":[{"value":"11 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16008"}}