{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:42:23Z","timestamp":1790329343521,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"am","delay-in-days":250,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32\u2010AR\u2010048522"],"award-info":[{"award-number":["T32\u2010AR\u2010048522"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23\u2010AR\u2010061439"],"award-info":[{"award-number":["K23\u2010AR\u2010061439"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50\u2010AR\u2010054144"],"award-info":[{"award-number":["P50\u2010AR\u2010054144"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K01\u2010AR\u2010067280"],"award-info":[{"award-number":["K01\u2010AR\u2010067280"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R03\u2010AR\u2010065801"],"award-info":[{"award-number":["R03\u2010AR\u2010065801"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P60\u2010AR\u2010062755"],"award-info":[{"award-number":["P60\u2010AR\u2010062755"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UL1\u2010RR\u2010029882"],"award-info":[{"award-number":["UL1\u2010RR\u2010029882"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UL1\u2010TR\u2010000062"],"award-info":[{"award-number":["UL1\u2010TR\u2010000062"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P60\u2010AR\u2010062755"],"award-info":[{"award-number":["P60\u2010AR\u2010062755"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01\u2010NR\u2010013888"],"award-info":[{"award-number":["R01\u2010NR\u2010013888"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K24\u2010AR\u2010063120"],"award-info":[{"award-number":["K24\u2010AR\u2010063120"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001845","name":"Scleroderma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001845","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"\n Objective<\/jats:title>\n \n Whole\u2010exome sequencing (\n WES<\/jats:styled-content>\n ) studies in systemic sclerosis (\n SS<\/jats:styled-content>\n c) patients of European American (\n EA<\/jats:styled-content>\n ) ancestry have identified variants in the\n \n ATP<\/jats:styled-content>\n 8B4\n <\/jats:italic>\n gene and enrichment of variants in genes in the extracellular matrix (\n ECM<\/jats:styled-content>\n )\u2013related pathway that increase\n SS<\/jats:styled-content>\n c susceptibility. This study was undertaken to evaluate the association of the\n \n ATP<\/jats:styled-content>\n 8B4\n <\/jats:italic>\n gene and the\n ECM<\/jats:styled-content>\n \u2010related pathway with\n SS<\/jats:styled-content>\n c in a cohort of African American (\n AA<\/jats:styled-content>\n ) patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n SS<\/jats:styled-content>\n c patients of\n AA<\/jats:styled-content>\n ancestry were enrolled from 23 academic centers across the\n US<\/jats:styled-content>\n under the Genome Research in African American Scleroderma Patients consortium. Unrelated\n AA<\/jats:styled-content>\n individuals without serologic evidence of autoimmunity who were enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the 2\n WES<\/jats:styled-content>\n studies in\n EA<\/jats:styled-content>\n patients with\n SS<\/jats:styled-content>\n c were selected for gene association testing using the optimized sequence kernel association test (\n SKAT<\/jats:styled-content>\n \u2010O) and pathway analysis by Ingenuity Pathway Analysis in 379 patients and 411 controls.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds, with roughly equal proportions of mean European admixture. Using\n SKAT<\/jats:styled-content>\n \u2010O, we examined the association of individual genes that were previously reported in\n EA<\/jats:styled-content>\n patients and none remained significant, including\n \n ATP<\/jats:styled-content>\n 8B4\n <\/jats:italic>\n (\n P<\/jats:italic>\n = 0.98). However, we confirmed the previously reported association of the\n ECM<\/jats:styled-content>\n \u2010related pathway with enrichment of variants within the\n \n COL<\/jats:styled-content>\n 13A1\n <\/jats:italic>\n ,\n \n COL<\/jats:styled-content>\n 18A1\n <\/jats:italic>\n ,\n \n COL<\/jats:styled-content>\n 22A1\n <\/jats:italic>\n ,\n \n COL<\/jats:styled-content>\n 4A3\n <\/jats:italic>\n ,\n \n COL<\/jats:styled-content>\n 4A4\n <\/jats:italic>\n ,\n \n COL<\/jats:styled-content>\n 5A2\n <\/jats:italic>\n ,\n \n PROK<\/jats:styled-content>\n 1\n <\/jats:italic>\n , and\n \n SERPINE<\/jats:styled-content>\n 1\n <\/jats:italic>\n genes (corrected\n P<\/jats:italic>\n = 1.95 \u00d7 10\n \u22124<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In the largest genetic study in\n AA<\/jats:styled-content>\n patients with\n SS<\/jats:styled-content>\n c to date, our findings corroborate the role of functional variants that aggregate in a fibrotic pathway and increase\n SS<\/jats:styled-content>\n c susceptibility.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40541","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T01:11:17Z","timestamp":1525655477000},"page":"1654-1660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Brief Report: Whole\u2010Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6488-1850","authenticated-orcid":false,"given":"Pravitt","family":"Gourh","sequence":"first","affiliation":[{"name":"NIAMS and National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9522-1249","authenticated-orcid":false,"given":"Elaine F.","family":"Remmers","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Boyden","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Alexander","sequence":"additional","affiliation":[{"name":"NIAMS NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia D.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2009","authenticated-orcid":false,"given":"Ami A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[{"name":"University of Texas McGovern Medical School Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayo","family":"Doumatey","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Bentley","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Shriner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn T.","family":"Domsic","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Thomas A.","family":"Medsger","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia D.","family":"Steen","sequence":"additional","affiliation":[{"name":"Georgetown University School of Medicine Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula S.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Silver","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Korman","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Varga","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Schiopu","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Khanna","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"Hsu","sequence":"additional","affiliation":[{"name":"Robert Wood Johnson University New Brunswick New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-0592","authenticated-orcid":false,"given":"Jessica K.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley Ann","family":"Saketkoo","sequence":"additional","affiliation":[{"name":"Tulane University School of Medicine New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Gladue","sequence":"additional","affiliation":[{"name":"Arthritis and Osteoporosis Consultants of the Carolinas Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brynn","family":"Kron","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"}]},{"given":"Chris T.","family":"Derk","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-1389","authenticated-orcid":false,"suffix":"Jr.","given":"S. Louis","family":"Bridges","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria K.","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"The George Washington University Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen D.","family":"Kolstad","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorinda","family":"Chung","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Stanford, California and Palo Alto VA Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Jan","sequence":"additional","affiliation":[{"name":"University of Chicago Pritzker School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-6390","authenticated-orcid":false,"given":"Elana J.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"New York Presbyterian Hospital Columbia University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avram","family":"Goldberg","sequence":"additional","affiliation":[{"name":"New York University Langone Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Trojanowski","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Kafaja","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine University of California Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Maksimowicz\u2010McKinnon","sequence":"additional","affiliation":[{"name":"Henry Ford Health System Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Mullikin","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Intramural Sequencing Center Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebowale","family":"Adeyemo","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Rotimi","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Boin","sequence":"additional","affiliation":[{"name":"University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute NIH Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11073"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.04.031"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-017-3826-y"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1359::AID-ART228>3.0.CO;2-S"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.565"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39449"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39721"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.111906"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008980"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000564"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.094052.109"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.23"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40058"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40541","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40541","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.40541","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/art.40541","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:44:35Z","timestamp":1759949075000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":15,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/art.40541"],"URL":"https:\/\/doi.org\/10.1002\/art.40541","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,29]]},"assertion":[{"value":"2018-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}