{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:13:18Z","timestamp":1793304798718,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014247","name":"Immune Tolerance Network","doi-asserted-by":"publisher","award":["UM1AI109565"],"award-info":[{"award-number":["UM1AI109565"]}],"id":[{"id":"10.13039\/100014247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014247","name":"Immune Tolerance Network","doi-asserted-by":"publisher","award":["UM2AI117870"],"award-info":[{"award-number":["UM2AI117870"]}],"id":[{"id":"10.13039\/100014247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI104209"],"award-info":[{"award-number":["U19AI104209"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016667","name":"Sean N. Parker Center for Allergy and Asthma Research, Stanford University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012604","name":"Crown Family Philanthropies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012604","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In the Learning Early About Peanut Allergy (LEAP) study, participants in the peanut consumption group, at 60\u2009months of age, had higher levels of peanut\u2010specific IgG4 (psIgG4), a biomarker of immune modulation, compared to those in the peanut\u2010avoidance group. We investigated the genetic determinants of psIgG4 among participants who consumed peanuts. Using whole\u2010genome sequencing data, we performed a genome\u2010wide association study (GWAS) for psIgG4 in the LEAP peanut consumption group participants (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009267). We generated a cumulative genetic score from the identified loci and evaluated its association with psIgG4 levels in LEAP. The association was then assessed for replication in two independent peanut oral immunotherapy (PnOIT) trials, IMPACT and POISED. We identified 45 variants that reached suggestive significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20091\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ), mapping to 17 independent loci in the LEAP peanut consumption group; none of these variants were associated with the psIgG4 levels in the avoidance group, highlighting a potential gene\u2010by\u2010environment (GxE) interaction. One locus on chromosome 2 showed regulatory signatures for\n                    <jats:italic>SEPT2<\/jats:italic>\n                    , a gene involved in epithelial barrier function. The genetic score was significantly associated with psIgG4 among LEAP consumers (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u20090.433;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.20\u2009\u00d7\u200910\n                    <jats:sup>\u221258<\/jats:sup>\n                    ) in the discovery cohort and IMPACT PnOIT participants (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u20090.287;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) in an independent testing cohort. No association was observed in older POISED PnOIT participants (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.029;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.79). Identification of the\n                    <jats:italic>SEPT2<\/jats:italic>\n                    locus in participants protected from peanut allergy (PA) suggests involvement of epithelial barrier pathways in modulating immune responses. Findings across all three trials emphasise the importance of GxE interactions, specifically the interplay between genetics and oral peanut exposure. Taken together, the findings indicate that early, sustained peanut consumption, combined with genetic factors, promotes a protective immune response to peanut allergens.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    LEAP: NCT00329784; IMPACT: NCT03345160; POISED, NCT02103270\n                  <\/jats:p>","DOI":"10.1111\/imm.70098","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T15:46:18Z","timestamp":1769787978000},"page":"280-292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Determinants of Peanut\u2010Specific\n                    <scp>IgG4<\/scp>\n                    Levels in the Context of Sustained Oral Peanut Exposure in the\n                    <scp>LEAP<\/scp>\n                    Study"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4993-8841","authenticated-orcid":false,"given":"Kanika","family":"Kanchan","sequence":"first","affiliation":[{"name":"Genomics and Precision Health Section, Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Cerosaletti","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Perry","sequence":"additional","affiliation":[{"name":"Genomics and Precision Health Section, Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"DuToit","sequence":"additional","affiliation":[{"name":"The Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology King's College London, and Guy's and St. Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1869-2645","authenticated-orcid":false,"given":"Monali","family":"Manohar","sequence":"additional","affiliation":[{"name":"Sean N. Parker Center for Allergy and Asthma Research Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Ling","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Department of Medicine, School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin E.","family":"Paschall","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Department of Medicine, School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinath","family":"Sanda","sequence":"additional","affiliation":[{"name":"The Immune Tolerance Network  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Sharon","family":"Chinthrajah","sequence":"additional","affiliation":[{"name":"Sean N. Parker Center for Allergy and Asthma Research Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald T.","family":"Nepom","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason  Seattle Washington USA"},{"name":"The Immune Tolerance Network  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-2955","authenticated-orcid":false,"given":"Kari C.","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Division of Allergy and Inflammation Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3491-4815","authenticated-orcid":false,"given":"Stacie M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Allergy and Immunology University of Arkansas for Medical Sciences and Arkansas Children's Hospital  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Lack","sequence":"additional","affiliation":[{"name":"The Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology King's College London, and Guy's and St. Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Ruczinski","sequence":"additional","affiliation":[{"name":"Department 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