{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:08:00Z","timestamp":1790723280262,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["8UL1TR001866"],"award-info":[{"award-number":["8UL1TR001866"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-14-CE14- 0007-01"],"award-info":[{"award-number":["ANR-14-CE14- 0007-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-16-CE12-0023-01"],"award-info":[{"award-number":["ANR-16-CE12-0023-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"HHS | NIH | National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1HG006504"],"award-info":[{"award-number":["UM1HG006504"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["U24 HG008956"],"award-info":[{"award-number":["U24 HG008956"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,8,11]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Despite a growing number of reports of rare disorders not fully explained by monogenic lesions, digenic inheritance has been reported for only 54 diseases to date. The very few existing methods for detecting gene \u00d7 gene interactions from next-generation sequencing data were generally examined in rare-variant association studies with limited simulation analyses for short genomic regions, under a case-control design. We describe a case-only approach designed specifically to search for digenic inheritance, which avoids recruitment of controls. We show, through both extensive simulation studies on real whole-exome sequencing datasets and application to a real example of craniosynostosis, that our method is robust and powerful for the genome-wide identification of digenic lesions.<\/jats:p>","DOI":"10.1073\/pnas.1920650117","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T20:28:28Z","timestamp":1595881708000},"page":"19367-19375","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["A genome-wide case-only test for the detection of digenic inheritance in human exomes"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-9428","authenticated-orcid":false,"given":"Gaspard","family":"Kerner","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Bouaziz","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Cobat","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Bigio","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8926-9692","authenticated-orcid":false,"given":"Andrew T.","family":"Timberlake","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale University School of Medicine, New Haven, CT 06510;"},{"name":"HHMI, New York, NY 10065;"},{"name":"Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510;"},{"name":"Hansj\u00f6rg Wyss Department of Plastic Surgery, New York University Langone Medical Center, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-2482","authenticated-orcid":false,"given":"Jacinta","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"},{"name":"Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Lifton","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale University School of Medicine, New Haven, CT 06510;"},{"name":"HHMI, New York, NY 10065;"},{"name":"Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 06510;"},{"name":"Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"},{"name":"HHMI, New York, NY 10065;"},{"name":"Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Abel","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;"},{"name":"University of Paris, Imagine Institute, 75015 Paris, France;"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep46454"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3031"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.628"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1239101"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aau8714"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2868"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910672106"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.330.6006.903"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.08.003"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08250"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a001388"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63597"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001756"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1331-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13150"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101713"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1068"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2344"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20125"},{"key":"e_1_3_4_20_2","unstructured":"McKusick-Nathans Institute of Genetic Medicine Johns Hopkins University Online Mendelian Inheritance in Man. https:\/\/omim.org\/. Accessed 9 August 2019."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2463"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102822"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000125524.34234.13"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3144"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4352"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083057"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-018-0543-4"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.147"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/154.8.687"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/155.5.478"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1159\/000099183"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/gepi.20427","article-title":"Case-only genome-wide interaction study of disease risk, prognosis and treatment","volume":"34","author":"Pierce B. L.","year":"2010","unstructured":"B. L. Pierce, H. Ahsan, Case-only genome-wide interaction study of disease risk, prognosis and treatment. Genet. Epidemiol. 34, 7\u201315 (2010).","journal-title":"Genet. Epidemiol."},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199903000-00014"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.06.009"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.09.003"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","unstructured":"A. Belkadi . Whole-exome sequencing to analyze population structure parental inbreeding and familial linkage. Proc. Natl. Acad. Sci. U.S.A. https:\/\/doi.org\/10.1073\/pnas.1606460113 (2016).","DOI":"10.1073\/pnas.1606460113"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1497-2"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1920650117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1920650117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T17:56:15Z","timestamp":1723312575000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1920650117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,27]]},"references-count":38,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2020,8,11]]}},"alternative-id":["10.1073\/pnas.1920650117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1920650117","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.738394732.793578010","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.02.06.936922","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,27]]},"assertion":[{"value":"2020-07-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}