{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T18:16:22Z","timestamp":1783188982243,"version":"3.54.6"},"posted":{"date-parts":[[2026,6,30]]},"group-title":"Genetic and Genomic Medicine","reference-count":169,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["U19AI166059"],"award-info":[{"award-number":["U19AI166059"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["T32HG002536"],"award-info":[{"award-number":["T32HG002536"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014576","name":"University of California Office of the President","doi-asserted-by":"crossref","award":["VFR-19-633386"],"award-info":[{"award-number":["VFR-19-633386"]}],"id":[{"id":"10.13039\/100014576","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Coccidioidomycosis, also known as Valley Fever, is a fungal disease endemic to the Americas that kills hundreds annually, yet the host factors that lead to increased risk of life-threatening dissemination of coccidioidomycosis remain poorly understood. We assembled the largest comprehensively sequenced coccidioidomycosis cohort to date, comprising 795 individuals with laboratory confirmed coccidioidomycosis and clinical disease severity phenotyping, many with paired whole blood genomic and transcriptomic data. Individuals with greater than 50% African genetic ancestry have increased risk for disseminated coccidioidomycosis (DCM) cases (OR=13.37, p=1.08\u00d710\n                  <jats:sup>-18<\/jats:sup>\n                  ), reflecting ancestry-associated differences in allele frequencies at immune loci. Transcriptomic profiling (n=267) revealed upregulation of interferon-inducible genes\n                  <jats:italic>IFI44<\/jats:italic>\n                  and\n                  <jats:italic>IFI44L<\/jats:italic>\n                  , the fungal recognition receptor\n                  <jats:italic>CLEC4D<\/jats:italic>\n                  , and pro-inflammatory protein\n                  <jats:italic>S100A12<\/jats:italic>\n                  , with sex-specific expression differences in immune cell composition. Gene-burden testing identified NOD-like receptor NLRX1 as the only gene carrying significantly more damaging rare variants than expected by chance (p=5.85\u00d710\u207b\u2074). We identified a rare missense variant,\n                  <jats:italic>NLRX1<\/jats:italic>\n                  p.Arg252Trp (rs145644388), in five patients with DCM that represents a founder variant: all carriers share African local genetic ancestry and carry 0.6\u20131.1 centimorgans of identical-by-descent sequence, indicating origin from a common ancestor. In gnomAD,\n                  <jats:italic>NLRX1<\/jats:italic>\n                  p.Arg252Trp shows has higher allele frequency in African (AF=0.00615) compared to European (AF= 2.25x10\n                  <jats:sup>-5<\/jats:sup>\n                  ) populations, directly linking this rare variant to population-level African genetic ancestry enrichment in DCM.\n                  <jats:italic>NLRX1<\/jats:italic>\n                  disruption impairs LC3-associated phagocytosis, an antifungal mechanism in macrophages. Together, these findings reveal both immune gene expression dysregulation and rare-variant architectures associated with African genetic ancestry underlying severe coccidioidomycosis and identify new targets for risk stratification and treatment.\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"26356412v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Patients with disseminated coccidioidomycosis are significantly more likely to have African genetic ancestry.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Whole-blood transcriptomics identifies upregulation of interferon-inducible genes\n                        <jats:italic>IFI44<\/jats:italic>\n                        ,\n                        <jats:italic>IFI44L<\/jats:italic>\n                        , and fungal pattern-recognition receptor\n                        <jats:italic>CLEC4D<\/jats:italic>\n                        in disseminated disease.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Rare missense variants in\n                        <jats:italic>NLRX1<\/jats:italic>\n                        , a mitochondrial NOD-like receptor involved in LC3-associated phagocytosis, are significantly enriched in disseminated cases by gene-burden testing.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Context and Significance<\/jats:title>\n                  <jats:p>Valley fever (coccidioidomycosis) is a fungal infection endemic to the southwestern United States that causes life-threatening disseminated disease in a small fraction of those infected. The biological determinants underlying why some develop severe, disseminated infection remains poorly understood. Epidemiological studies have noted that individuals of African American or Filipino background face disproportionately higher risk for severe disease, but these studies relied on self-reported race, a social construct that is not biologically based. By assembling the largest genomically characterized Valley Fever cohort to date and using genome sequencing to directly quantify genetic ancestry, we show that genetic variation that is more common in populations with African ancestry is associated with risk for dissemination. We further identify disruption of interferon signaling and LC3-associated phagocytosis \u2014 a cellular mechanism by which macrophages contain fungal infections \u2014 as likely contributors to severe disease. These findings open new avenues for risk stratification and potential therapeutic targeting in this neglected fungal infection.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.26.26356412","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:35:03Z","timestamp":1782855303000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic and transcriptomic determinants of disseminated coccidioidomycosis identify a founder variant in\n                  <i>NLRX1<\/i>\n                  and ancestry-specific rare variants in immune response genes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-304X","authenticated-orcid":false,"given":"Samantha L.","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-0863","authenticated-orcid":false,"given":"Sarah J.","family":"Spendlove","sequence":"additional","affiliation":[{"name":"Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA"},{"name":"Kaiser Permanente Regional Molecular Genetic Pathology Laboratory, Southern California Permanente Medical Group, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-6838","authenticated-orcid":false,"given":"Alexis V.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2609-8206","authenticated-orcid":false,"given":"Zhenjie","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Dana-Farber Cancer Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-4901","authenticated-orcid":false,"given":"Varada","family":"Abhyankar","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-5596","authenticated-orcid":false,"given":"Kangcheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-7727","authenticated-orcid":false,"given":"Rachel","family":"Mester","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1729-816X","authenticated-orcid":false,"given":"Traci","family":"Toy","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-4758","authenticated-orcid":false,"given":"Eleazar","family":"Eskin","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8518-5750","authenticated-orcid":false,"suffix":"III","given":"George R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"UC Davis Center for Valley Fever, UC Davis, Davis, CA, USA"},{"name":"Department of Medical Microbiology and Immunology, UC Davis, Davis, CA, USA"},{"name":"Department of Medicine and Division of Infectious Diseases, UC Davis, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Royce H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Division of Infectious Diseases, Kern Medical, Bakersfield, CA, USA"},{"name":"Valley Fever Institute, Kern Medical, Bakersfield, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-348X","authenticated-orcid":false,"given":"Arash","family":"Heidari","sequence":"additional","affiliation":[{"name":"Dignity Health, Bakersfield Memorial Hospital, Bakersfield, CA, USA"},{"name":"Morehouse School of Medicine, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-2596","authenticated-orcid":false,"given":"Rasha","family":"Kuran","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Division of Infectious Diseases, Kern Medical, Bakersfield, CA, USA"},{"name":"Valley Fever Institute, Kern Medical, Bakersfield, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-6213","authenticated-orcid":false,"given":"Paul","family":"Krogstad","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0227-2056","authenticated-orcid":false,"given":"Bogdan","family":"Pasaniuc","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Computer and Information Science, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-2499","authenticated-orcid":false,"given":"Harold","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-5595","authenticated-orcid":false,"given":"Manish J.","family":"Butte","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, Los Angeles, CA, USA"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9687-9122","authenticated-orcid":false,"given":"Valerie A.","family":"Arboleda","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Computational Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070410300618000_2026.06.26.26356412v2.1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-022-00606-y"},{"key":"2026070410300618000_2026.06.26.26356412v2.2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2302.160505"},{"key":"2026070410300618000_2026.06.26.26356412v2.3","doi-asserted-by":"publisher","DOI":"10.1378\/chest.31.1.35"},{"key":"2026070410300618000_2026.06.26.26356412v2.4","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1295723"},{"key":"2026070410300618000_2026.06.26.26356412v2.5","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0b013e3181f378a8"},{"key":"2026070410300618000_2026.06.26.26356412v2.6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa188"},{"key":"2026070410300618000_2026.06.26.26356412v2.7","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad597"},{"key":"2026070410300618000_2026.06.26.26356412v2.8","doi-asserted-by":"publisher","DOI":"10.3201\/eid1811.120752"},{"key":"2026070410300618000_2026.06.26.26356412v2.9","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae454"},{"key":"2026070410300618000_2026.06.26.26356412v2.10","first-page":"217","article-title":"Increase in Reported Coccidioidomycosis \u2014 United States, 1998\u20132011","volume":"62","year":"2013","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"2026070410300618000_2026.06.26.26356412v2.11","doi-asserted-by":"publisher","DOI":"10.1029\/2019GH000209"},{"key":"2026070410300618000_2026.06.26.26356412v2.12","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7311a2"},{"key":"2026070410300618000_2026.06.26.26356412v2.13","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4857.290"},{"key":"2026070410300618000_2026.06.26.26356412v2.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08419.x"},{"key":"2026070410300618000_2026.06.26.26356412v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1104"},{"key":"2026070410300618000_2026.06.26.26356412v2.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg0928"},{"key":"2026070410300618000_2026.06.26.26356412v2.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246980"},{"key":"2026070410300618000_2026.06.26.26356412v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100151"},{"key":"2026070410300618000_2026.06.26.26356412v2.19","doi-asserted-by":"publisher","DOI":"10.1007\/BF02051481"},{"key":"2026070410300618000_2026.06.26.26356412v2.20","first-page":"16","article-title":"Coccidioidomycosis in Northern California\u2014An Outbreak among Archeology Students near Red Bluff","volume":"119","year":"1973","journal-title":"Calif. Med"},{"key":"2026070410300618000_2026.06.26.26356412v2.21","doi-asserted-by":"publisher","DOI":"10.1378\/chest.76.5.566"},{"key":"2026070410300618000_2026.06.26.26356412v2.22","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268809990999"},{"key":"2026070410300618000_2026.06.26.26356412v2.23","doi-asserted-by":"publisher","DOI":"10.3201\/eid2210.160696"},{"key":"2026070410300618000_2026.06.26.26356412v2.24","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2017.303820"},{"key":"2026070410300618000_2026.06.26.26356412v2.25","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab543"},{"key":"2026070410300618000_2026.06.26.26356412v2.26","doi-asserted-by":"publisher","DOI":"10.3390\/jof9070731"},{"key":"2026070410300618000_2026.06.26.26356412v2.27","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268820002836"},{"key":"2026070410300618000_2026.06.26.26356412v2.28","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0423"},{"key":"2026070410300618000_2026.06.26.26356412v2.29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201368"},{"key":"2026070410300618000_2026.06.26.26356412v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.03.004"},{"key":"2026070410300618000_2026.06.26.26356412v2.31","doi-asserted-by":"publisher","DOI":"10.1080\/00362177985380381"},{"key":"2026070410300618000_2026.06.26.26356412v2.32","doi-asserted-by":"publisher","DOI":"10.3201\/eid0505.990508"},{"key":"2026070410300618000_2026.06.26.26356412v2.33","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.866407"},{"key":"2026070410300618000_2026.06.26.26356412v2.34","unstructured":"Genome-Wide Association Study of Patients with Coccidioidomycosis dbGaP. https:\/\/www.ncbi.nlm.nih.gov\/projects\/gap\/cgi-bin\/study.cgi?study_id=phs002170.v1.p1."},{"key":"2026070410300618000_2026.06.26.26356412v2.35","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159491"},{"key":"2026070410300618000_2026.06.26.26356412v2.36","doi-asserted-by":"publisher","DOI":"10.1038\/7701"},{"key":"2026070410300618000_2026.06.26.26356412v2.37","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq215"},{"key":"2026070410300618000_2026.06.26.26356412v2.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.052"},{"key":"2026070410300618000_2026.06.26.26356412v2.39","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31819866ec"},{"key":"2026070410300618000_2026.06.26.26356412v2.40","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.199941"},{"key":"2026070410300618000_2026.06.26.26356412v2.41","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-23-3-349"},{"key":"2026070410300618000_2026.06.26.26356412v2.42","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.36.12.1394"},{"key":"2026070410300618000_2026.06.26.26356412v2.43","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1979.120.4.959"},{"key":"2026070410300618000_2026.06.26.26356412v2.44","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000126762.91040.fd"},{"key":"2026070410300618000_2026.06.26.26356412v2.45","doi-asserted-by":"publisher","DOI":"10.7205\/MILMED.173.8.769"},{"key":"2026070410300618000_2026.06.26.26356412v2.46","unstructured":"U.S. Census Bureau (2020). HISPANIC OR LATINO, AND NOT HISPANIC OR LATINO BY RACE. (Decennial Census). https:\/\/data.census.gov\/table\/DECENNIALPL2020.P2?g=040XX00US06_050XX00US060 29,06113&y=2020&d=DEC Redistricting Data (PL 94-171) https:\/\/data.census.gov\/table\/DECENNIALPL2020.P2?g=040XX00US06_050XX00US060 29,06113&y=2020&d=DEC Redistricting Data (PL 94-171)."},{"key":"2026070410300618000_2026.06.26.26356412v2.47","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae148"},{"key":"2026070410300618000_2026.06.26.26356412v2.48","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm7530"},{"key":"2026070410300618000_2026.06.26.26356412v2.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.05.001"},{"key":"2026070410300618000_2026.06.26.26356412v2.50","doi-asserted-by":"publisher","DOI":"10.1101\/gr.094052.109"},{"key":"2026070410300618000_2026.06.26.26356412v2.51","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.262172"},{"key":"2026070410300618000_2026.06.26.26356412v2.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.01.026"},{"key":"2026070410300618000_2026.06.26.26356412v2.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01980-4"},{"key":"2026070410300618000_2026.06.26.26356412v2.54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1029"},{"key":"2026070410300618000_2026.06.26.26356412v2.55","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-021-07909-3"},{"key":"2026070410300618000_2026.06.26.26356412v2.56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00142"},{"key":"2026070410300618000_2026.06.26.26356412v2.57","doi-asserted-by":"publisher","DOI":"10.70962\/jhi.20250003"},{"key":"2026070410300618000_2026.06.26.26356412v2.58","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2007.0021"},{"key":"2026070410300618000_2026.06.26.26356412v2.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.046"},{"key":"2026070410300618000_2026.06.26.26356412v2.60","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01839-19"},{"key":"2026070410300618000_2026.06.26.26356412v2.61","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00297-20"},{"key":"2026070410300618000_2026.06.26.26356412v2.62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1013322"},{"key":"2026070410300618000_2026.06.26.26356412v2.63","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5599408"},{"key":"2026070410300618000_2026.06.26.26356412v2.64","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa341"},{"key":"2026070410300618000_2026.06.26.26356412v2.65","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-07134-5"},{"key":"2026070410300618000_2026.06.26.26356412v2.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109979"},{"key":"2026070410300618000_2026.06.26.26356412v2.67","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2008.23"},{"key":"2026070410300618000_2026.06.26.26356412v2.68","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00597-12"},{"key":"2026070410300618000_2026.06.26.26356412v2.69","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.4159-4171.2004"},{"key":"2026070410300618000_2026.06.26.26356412v2.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.017"},{"key":"2026070410300618000_2026.06.26.26356412v2.71","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.588574"},{"key":"2026070410300618000_2026.06.26.26356412v2.72","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500041-MCP200"},{"key":"2026070410300618000_2026.06.26.26356412v2.73","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6191-2_5"},{"key":"2026070410300618000_2026.06.26.26356412v2.74","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.714026"},{"key":"2026070410300618000_2026.06.26.26356412v2.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91754-7"},{"key":"2026070410300618000_2026.06.26.26356412v2.76","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747161"},{"key":"2026070410300618000_2026.06.26.26356412v2.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2017.09.031"},{"key":"2026070410300618000_2026.06.26.26356412v2.78","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010479"},{"key":"2026070410300618000_2026.06.26.26356412v2.79","doi-asserted-by":"publisher","DOI":"10.1080\/08830185.2021.1931171"},{"key":"2026070410300618000_2026.06.26.26356412v2.80","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01194-10"},{"key":"2026070410300618000_2026.06.26.26356412v2.81","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i44.9813"},{"key":"2026070410300618000_2026.06.26.26356412v2.82","doi-asserted-by":"publisher","DOI":"10.1186\/s41065-020-00167-5"},{"key":"2026070410300618000_2026.06.26.26356412v2.83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1060438"},{"key":"2026070410300618000_2026.06.26.26356412v2.84","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28706"},{"key":"2026070410300618000_2026.06.26.26356412v2.85","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1470924"},{"key":"2026070410300618000_2026.06.26.26356412v2.86","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60949-1"},{"key":"2026070410300618000_2026.06.26.26356412v2.87","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_12"},{"key":"2026070410300618000_2026.06.26.26356412v2.88","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-08844-9"},{"key":"2026070410300618000_2026.06.26.26356412v2.89","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx4381"},{"key":"2026070410300618000_2026.06.26.26356412v2.90","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.2.265"},{"key":"2026070410300618000_2026.06.26.26356412v2.91","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.8.3376-3380.1997"},{"key":"2026070410300618000_2026.06.26.26356412v2.92","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.7011-7013.2005"},{"key":"2026070410300618000_2026.06.26.26356412v2.93","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.581101"},{"key":"2026070410300618000_2026.06.26.26356412v2.94","doi-asserted-by":"publisher","DOI":"10.1086\/605532"},{"key":"2026070410300618000_2026.06.26.26356412v2.95","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159348"},{"key":"2026070410300618000_2026.06.26.26356412v2.96","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150632"},{"key":"2026070410300618000_2026.06.26.26356412v2.97","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20191519"},{"key":"2026070410300618000_2026.06.26.26356412v2.98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2016.04.040"},{"key":"2026070410300618000_2026.06.26.26356412v2.99","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3562-2"},{"key":"2026070410300618000_2026.06.26.26356412v2.100","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.007"},{"key":"2026070410300618000_2026.06.26.26356412v2.101","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6023607"},{"key":"2026070410300618000_2026.06.26.26356412v2.102","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401161"},{"key":"2026070410300618000_2026.06.26.26356412v2.103","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.022"},{"key":"2026070410300618000_2026.06.26.26356412v2.104","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00363"},{"key":"2026070410300618000_2026.06.26.26356412v2.105","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13291"},{"key":"2026070410300618000_2026.06.26.26356412v2.106","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008854"},{"key":"2026070410300618000_2026.06.26.26356412v2.107","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02761"},{"key":"2026070410300618000_2026.06.26.26356412v2.108","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.749504"},{"key":"2026070410300618000_2026.06.26.26356412v2.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.025"},{"key":"2026070410300618000_2026.06.26.26356412v2.110","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-022-05415-3"},{"key":"2026070410300618000_2026.06.26.26356412v2.111","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201600034"},{"key":"2026070410300618000_2026.06.26.26356412v2.112","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005116"},{"key":"2026070410300618000_2026.06.26.26356412v2.113","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2021.07.006"},{"key":"2026070410300618000_2026.06.26.26356412v2.114","doi-asserted-by":"publisher","DOI":"10.1128\/iai.34.2.347-353.1981"},{"key":"2026070410300618000_2026.06.26.26356412v2.115","doi-asserted-by":"publisher","DOI":"10.1177\/2324709620949315"},{"key":"2026070410300618000_2026.06.26.26356412v2.116","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.10.4552-4555.2004"},{"key":"2026070410300618000_2026.06.26.26356412v2.117","unstructured":"Nguyen, A. , Sondermeyer Cooksey, G. , Djamba, Y. , Nicolici, A. , and Vugia, D . (2022). Epidemiologic Summary of Valley Fever (Coccidioidomycosis) in California, 2020-2021 (Surveillance and Statistics Section, Infectious Diseases Branch, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health)."},{"key":"2026070410300618000_2026.06.26.26356412v2.118","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"2026070410300618000_2026.06.26.26356412v2.119","unstructured":"Lift Genome Annotations https:\/\/genome.ucsc.edu\/cgi-bin\/hgLiftOver."},{"key":"2026070410300618000_2026.06.26.26356412v2.120","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"2026070410300618000_2026.06.26.26356412v2.121","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"2026070410300618000_2026.06.26.26356412v2.122","unstructured":"TOPMed Freeze 5 Version Freeze 5. https:\/\/bravo.sph.umich.edu\/freeze5\/hg38\/download\/all https:\/\/bravo.sph.umich.edu\/freeze5\/hg38\/download\/all."},{"key":"2026070410300618000_2026.06.26.26356412v2.123","unstructured":"Rayner, W. CreateTOPMed.pl."},{"key":"2026070410300618000_2026.06.26.26356412v2.124","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3679"},{"key":"2026070410300618000_2026.06.26.26356412v2.125","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu704"},{"key":"2026070410300618000_2026.06.26.26356412v2.126","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"2026070410300618000_2026.06.26.26356412v2.127","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"2026070410300618000_2026.06.26.26356412v2.128","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq559"},{"key":"2026070410300618000_2026.06.26.26356412v2.129","doi-asserted-by":"publisher","DOI":"10.1038\/nature18964"},{"key":"2026070410300618000_2026.06.26.26356412v2.130","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5012"},{"key":"2026070410300618000_2026.06.26.26356412v2.131","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.08.004"},{"key":"2026070410300618000_2026.06.26.26356412v2.132","doi-asserted-by":"publisher","DOI":"10.1101\/gr.278378.123"},{"key":"2026070410300618000_2026.06.26.26356412v2.133","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"2026070410300618000_2026.06.26.26356412v2.134","unstructured":"Price, A. , Patterson, N. , and Mah, M . (2014). EIGENSOFT. Version 6.0.1 (David Reich Lab)."},{"key":"2026070410300618000_2026.06.26.26356412v2.135","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01415-w"},{"key":"2026070410300618000_2026.06.26.26356412v2.136","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.020"},{"key":"2026070410300618000_2026.06.26.26356412v2.137","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr917"},{"key":"2026070410300618000_2026.06.26.26356412v2.138","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"2026070410300618000_2026.06.26.26356412v2.139","doi-asserted-by":"publisher","DOI":"10.1101\/164343"},{"key":"2026070410300618000_2026.06.26.26356412v2.140","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz235"},{"key":"2026070410300618000_2026.06.26.26356412v2.141","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2026070410300618000_2026.06.26.26356412v2.142","unstructured":"Bushnell, B . (2014). BBMap: A Fast, Accurate, Splice-Aware Aligner."},{"key":"2026070410300618000_2026.06.26.26356412v2.143","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026070410300618000_2026.06.26.26356412v2.144","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026070410300618000_2026.06.26.26356412v2.145","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqaa078"},{"key":"2026070410300618000_2026.06.26.26356412v2.146","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf018"},{"key":"2026070410300618000_2026.06.26.26356412v2.147","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026070410300618000_2026.06.26.26356412v2.148","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bau012"},{"key":"2026070410300618000_2026.06.26.26356412v2.149","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx922"},{"key":"2026070410300618000_2026.06.26.26356412v2.150","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bay003"},{"key":"2026070410300618000_2026.06.26.26356412v2.151","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1055"},{"key":"2026070410300618000_2026.06.26.26356412v2.152","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"2026070410300618000_2026.06.26.26356412v2.153","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baac019"},{"key":"2026070410300618000_2026.06.26.26356412v2.154","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad960"},{"key":"2026070410300618000_2026.06.26.26356412v2.155","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1005"},{"key":"2026070410300618000_2026.06.26.26356412v2.156","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1025"},{"key":"2026070410300618000_2026.06.26.26356412v2.157","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1082"},{"key":"2026070410300618000_2026.06.26.26356412v2.158","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1010"},{"key":"2026070410300618000_2026.06.26.26356412v2.159","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae909"},{"key":"2026070410300618000_2026.06.26.26356412v2.160","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00702"},{"key":"2026070410300618000_2026.06.26.26356412v2.161","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"2026070410300618000_2026.06.26.26356412v2.162","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"2026070410300618000_2026.06.26.26356412v2.163","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0301-7_7"},{"key":"2026070410300618000_2026.06.26.26356412v2.164","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt607"},{"key":"2026070410300618000_2026.06.26.26356412v2.165","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab314"},{"key":"2026070410300618000_2026.06.26.26356412v2.166","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"2026070410300618000_2026.06.26.26356412v2.167","doi-asserted-by":"publisher","DOI":"10.1110\/ps.072791207"},{"key":"2026070410300618000_2026.06.26.26356412v2.168","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bar030"},{"key":"2026070410300618000_2026.06.26.26356412v2.169","unstructured":"phase_rare (2024). SHAPEIT5. https:\/\/web.archive.org\/web\/20240917105217\/https:\/\/odelaneau.github.io\/shapeit5\/docs\/documentation\/phase_rare\/."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.26.26356412","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T17:30:19Z","timestamp":1783186219000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.06.26.26356412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":169,"URL":"https:\/\/doi.org\/10.64898\/2026.06.26.26356412","relation":{},"subject":[],"published":{"date-parts":[[2026,6,30]]},"subtype":"preprint"}}