{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:25:28Z","timestamp":1790256328561,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n            <jats:title>Purpose of review<\/jats:title>\n            <jats:p>This article reviews the progress in the search for the genetic determinants of severe asthma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Recent findings<\/jats:title>\n            <jats:p>Twin studies estimate that approximately 25% of the phenotypic variability in asthma severity is determined by genetic factors, with the remainder determined by nongenetic factors including environmental and psychosocial factors, behavioral traits, and comorbidities. Most genetic association studies of asthma severity performed to date are underpowered and not designed to clearly distinguish asthma severity variants from asthma susceptibility variants. However, the most recent genome-wide asthma severity association study, conducted in more than 57\u200a000 individuals, demonstrated significant associations for 25 loci, including three not previously associated with asthma: GATA3, MUC5AC, and KIAA1109. Of these, the MUC5AC association was restricted to cohorts that included moderate-to-severe (but not mild) asthma. Additional insights from rare monogenic disorders that can present as severe asthma include recognition that loss-of-function variants in the <jats:italic toggle=\"yes\">filaggrin<\/jats:italic> gene known to cause ichthyosis vulgaris are consistently associated with more severe asthma outcomes. Other notable loci of interest include RAD50-IL13 on chromosome 5q and the ORMDL3-GSDMB locus on chromosome 17q21.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Summary<\/jats:title>\n            <jats:p>Severe asthma is a polygenic trait. Future research should explore the role of rare genetic variation and gene-by-environment interaction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/mop.0000000000000758","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T19:20:18Z","timestamp":1554232818000},"page":"340-348","source":"Crossref","is-referenced-by-count":17,"title":["Asthma severity, nature or nurture: genetic determinants"],"prefix":"10.1097","volume":"31","author":[{"given":"Benjamin A.","family":"Raby","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, Boston Children's Hospital"},{"name":"Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital"},{"name":"Harvard Medical School, Boston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230918","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jaip.2015.10.008","article-title":"Severe asthma in children: lessons learned and future directions","volume":"4","author":"Fitzpatrick","year":"2016","journal-title":"J Allergy Clin Immunol Pract"},{"key":"R2-20230918","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12931-018-0855-3","article-title":"Healthcare resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR)","volume":"19","author":"Janson","year":"2018","journal-title":"Respir Res"},{"key":"R3-20230918","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1183\/09031936.04.00004904","article-title":"Asthma severity and medical resource utilisation","volume":"23","author":"Antonicelli","year":"2004","journal-title":"Eur Respir J"},{"key":"R4-20230918","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ped.2018.0901","article-title":"Current state and future of biologic therapies in the treatment of asthma in children","volume":"31","author":"Abrams","year":"2018","journal-title":"Pediatr Allergy Immunol Pulmonol"},{"key":"R5-20230918","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2147\/JAA.S135291","article-title":"Bronchial thermoplasty: implementing best practice in the era of cost containment","volume":"10","author":"Tan","year":"2017","journal-title":"J Asthma Allergy"},{"key":"R6-20230918","first-page":"1","article-title":"Economic impact of severe asthma in Spain: multicentre observational longitudinal study","author":"Melero Moreno","year":"2018","journal-title":"J Asthma"},{"key":"R7-20230918","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.1164\/rccm.201810-1895ST","article-title":"Current status and future opportunities in lung precision medicine research with a focus on biomarkers. 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