{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:52:24Z","timestamp":1792878744220,"version":"4.5.0"},"reference-count":45,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["201921080"],"award-info":[{"award-number":["201921080"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["201980204"],"award-info":[{"award-number":["201980204"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2020,6,25]]},"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:p>\n                    Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype in\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    , is one of the most common inherited diseases. Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.\n                  <\/jats:p>\n                  <jats:p>\n                    We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality. A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes. A polygenic risk score (PRS) for forced expiratory volume in 1\u2005s (FEV\n                    <jats:sub>1<\/jats:sub>\n                    )\/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.\n                  <\/jats:p>\n                  <jats:p>\n                    Among 458\u200a164 European-ancestry participants in UK Biobank, 140 had the PI*ZZ genotype and only nine (6.4%, 95% CI 3.4\u201311.7%) of them were diagnosed with AATD. Those with PI*ZZ had a substantially higher odds of COPD (OR 8.8, 95% CI 5.8\u201313.3), asthma (OR 2.0, 95% CI 1.4\u20133.0), bronchiectasis (OR 7.3, 95%CI 3.2\u201316.8), pneumonia (OR 2.7, 95% CI 1.5\u20134.9) and cirrhosis (OR 7.8, 95% CI 2.5\u201324.6) diagnoses and a higher hazard of mortality (2.4, 95% CI 1.2\u20134.6), compared to PI*MM (wildtype) (n=398\u200a424). These associations were stronger among smokers. PheWAS demonstrated associations with increased odds of empyema, pneumothorax, cachexia, polycythaemia, aneurysm and pancreatitis. Polygenic risk score and PI*ZZ were independently associated with FEV\n                    <jats:sub>1<\/jats:sub>\n                    \/FVC &lt;0.7 (OR 1.4 per 1-\n                    <jats:sc>sd<\/jats:sc>\n                    change, 95% CI 1.4\u20131.5 and OR 4.5, 95% CI 3.0\u20136.9, respectively).\n                  <\/jats:p>\n                  <jats:p>The important underdiagnosis of AATD, whose outcomes are partially preventable through smoking cession, could be improved through genotype-guided diagnosis.<\/jats:p>","DOI":"10.1183\/13993003.01441-2020","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T16:45:14Z","timestamp":1594917914000},"page":"2001441","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":68,"title":["The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes"],"prefix":"10.1183","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-5646","authenticated-orcid":false,"given":"Tomoko","family":"Nakanishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-4720","authenticated-orcid":false,"given":"Vincenzo","family":"Forgetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-6412","authenticated-orcid":false,"given":"Tomohiro","family":"Handa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyohiro","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Mooser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Mark","family":"Lathrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9551-4677","authenticated-orcid":false,"given":"William O.C.M.","family":"Cookson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-9086","authenticated-orcid":false,"given":"J. 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