{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:03:27Z","timestamp":1792782207614,"version":"4.5.0"},"reference-count":14,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"University of California, San Francisco Institute for Human Genetics pilot grant and the Scleroderma Research Foundation","id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH","award":["T32-AR-007175"],"award-info":[{"award-number":["T32-AR-007175"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"\n Objective<\/jats:title>\n Scleroderma is a genetically complex autoimmune disease with substantial phenotypic heterogeneity. Previous genome\u2010wide association studies have identified common genetic variants associated with disease risk, but these studies are not designed to capture rare or potential causal variants. Our goal was to identify rare as well as common genetic variants in patients with diffuse cutaneous systemic sclerosis (dcSSc) through whole\u2010exome sequencing (WES) in order to identify potential causal variants.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We generated WES data for 32 dcSSc patients with or without interstitial lung disease (ILD) and for 17 healthy \u201cin\u2010house\u201d controls. Variants were annotated and filtered by quality, minor allele frequency, and deleterious effects on gene function. We applied a gene burden test to identify novel dcSSc and dcSSc\u2010associated ILD candidate genes that were enriched with deleterious variants in cases compared to in\u2010house controls as well as controls from the 1000 Genomes Project (n\u2009=\u2009130).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 70 genes that were enriched with deleterious variants in dcSSc patients. Two of them (\n BANK1<\/jats:italic>\n and\n TERT<\/jats:italic>\n ) were in pathways previously implicated in SSc or ILD pathogenesis or known susceptibility loci. Newly identified genes (\n COL4A3, COL4A4, COL5A2, COL13A1,<\/jats:italic>\n and\n COL22A1<\/jats:italic>\n ) were significantly enriched in the extracellular matrix\u2013related pathway, which is relevant to the fibrotic features of dcSSc, and in the DNA repair pathway (\n XRCC4<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study demonstrates the value of WES for the identification of novel gene variants and pathways that may contribute to scleroderma risk and\/or severity. The candidate genes we discovered are potential targets for in\u2010depth functional studies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.39721","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T20:22:48Z","timestamp":1461615768000},"page":"2257-2262","source":"Crossref","is-referenced-by-count":39,"title":["Brief Report: Whole\u2010Exome Sequencing for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis"],"prefix":"10.1002","volume":"68","author":[{"given":"Angel C. Y.","family":"Mak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L. F.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Cleveland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie H.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kari Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamiko R.","family":"Katsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Wolters","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui\u2010Yan","family":"Kwok","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey A.","family":"Criswell","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11073"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-010-8198-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-014-0484-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_8_6_1","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis","volume":"15","author":"LeRoy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2009-040GL"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr667"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217876"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39449"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24885"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.118174"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.79"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38702"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130376"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39721","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.39721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:55:07Z","timestamp":1791856507000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,25]]},"references-count":14,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/art.39721"],"URL":"https:\/\/doi.org\/10.1002\/art.39721","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,25]]}}}