{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:36:11Z","timestamp":1762079771907,"version":"3.37.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"British Medical Research Council","doi-asserted-by":"crossref","award":["MR\/N017390\/1"],"award-info":[{"award-number":["MR\/N017390\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006675","name":"National Institute of Science and Technology in Tropical Diseases","doi-asserted-by":"publisher","award":["573839\/2008\u20135"],"award-info":[{"award-number":["573839\/2008\u20135"]}],"id":[{"id":"10.13039\/501100006675","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI 30639"],"award-info":[{"award-number":["AI 30639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102858\/Z\/13\/Z"],"award-info":[{"award-number":["102858\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4\u2009498\u2009586 imputed single-nucleotide variants (SNVs). A genome-wide association study (GWAS) using linear mixed models took account of genetic diversity\/ethnicity\/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL) and chromatin interaction mapping was performed in Functional Mapping and Annotation (FUMA). Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Positional mapping identified 32 genomic loci associated with CL, none achieving genome-wide significance (P &amp;lt; 5 \u00d7 10\u22128). Lead SNVs at 23 loci occurred at protein coding or noncoding RNA genes, 15 with eQTLs for functionally relevant cells\/tissues and\/or showing differential expression in lesions. Of these, the 6 most plausible genetic risk loci were SERPINB10 (Pimputed_1000G = 2.67 \u00d7 10\u22126), CRLF3 (Pimputed_1000G = 5.12 \u00d7 10\u22126), STX7 (Pimputed_1000G = 6.06 \u00d7 10\u22126), KRT80 (Pimputed_1000G = 6.58 \u00d7 10\u22126), LAMP3 (Pimputed_1000G = 6.54 \u00d7 10\u22126), and IFNG-AS1 (Pimputed_1000G = 1.32 \u00d7 10\u22125). LAMP3 (Padjusted = 9.25 \u00d7 10\u221212; +6-fold), STX7 (Padjusted = 7.62 \u00d7 10\u22123; +1.3-fold), and CRLF3 (Padjusted = 9.19 \u00d7 10\u22129; +1.97-fold) were expressed more highly in CL biopsies compared to normal skin; KRT80 (Padjusted = 3.07 \u00d7 10\u22128; \u22123-fold) was lower. Multiple cis-eQTLs across SERPINB10 mapped to chromatin interaction regions of transcriptional\/enhancer activity in neutrophils, monocytes, B cells, and hematopoietic stem cells. Those at IFNG-AS1 mapped to transcriptional\/enhancer regions in T, natural killer, and B cells. The percentage of peripheral blood CD3+ T cells making antigen-specific interferon-\u03b3 differed significantly by IFNG-AS1 genotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This first GWAS for CL identified multiple genetic risk loci including a novel lead to understanding CL pathogenesis through regulation of interferon-\u03b3 by IFNG antisense RNA 1.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1230","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T11:57:13Z","timestamp":1597751833000},"page":"e515-e525","source":"Crossref","is-referenced-by-count":23,"title":["A Genome-wide Association Study Identifies <i>SERPINB10, CRLF3, STX7<\/i>, <i>LAMP3, IFNG-AS1<\/i>, and <i>KRT80<\/i> As Risk Loci Contributing to Cutaneous Leishmaniasis in Brazil"],"prefix":"10.1093","volume":"72","author":[{"given":"L\u00e9a C","family":"Castellucci","sequence":"first","affiliation":[{"name":"National Institute of Science and Technology in Tropical Diseases, Brazil"},{"name":"Federal University of Bahia, Salvador, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Almeida","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology in Tropical Diseases, Brazil"},{"name":"Federal University of Bahia, Salvador, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Cherlin","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Newcastle University, Newcastle-Upon-Tyne, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Fakiola","sequence":"additional","affiliation":[{"name":"National Institute of Molecular Genetics \u201cRomeo ed Enrica Invernizzi,\u201d Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W","family":"Francis","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute, University of Western Australia, Nedlands, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar M","family":"Carvalho","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology in Tropical Diseases, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anad\u00edlton","family":"Santos da Hora","sequence":"additional","affiliation":[{"name":"Federal University of Bahia, Salvador, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tain\u00e3 Souza","family":"do Lago","sequence":"additional","affiliation":[{"name":"Federal University of Bahia, Salvador, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda B","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"International Center for Research, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara M","family":"Cavalcanti","sequence":"additional","affiliation":[{"name":"International Center for Research, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia S","family":"Alves","sequence":"additional","affiliation":[{"name":"International Center for Research, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia L P","family":"Morais","sequence":"additional","affiliation":[{"name":"International Center for Research, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9a","family":"Teixeira-Carvalho","sequence":"additional","affiliation":[{"name":"Instituto Rene Rachou of Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ-Minas), Belo Horizonte, 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