{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:58:43Z","timestamp":1790243923126,"version":"4.1.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:sec id=\"ab-joi240141-4\"><jats:title>Importance<\/jats:title><jats:p>Chronic obstructive pulmonary disease (COPD) is often undiagnosed. Although genetic risk plays a significant role in COPD susceptibility, its utility in guiding spirometry testing and identifying undiagnosed cases is unclear.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-5\"><jats:title>Objective<\/jats:title><jats:p>To determine whether a COPD polygenic risk score (PRS) enhances the identification of undiagnosed COPD beyond a case-finding questionnaire (eg, the Lung Function Questionnaire) using conventional risk factors and respiratory symptoms.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cross-sectional analysis of participants 35 years or older who reported no history of physician-diagnosed COPD was conducted using data from 2 observational studies: the community-based Framingham Heart Study (FHS) and the COPD-enriched Genetic Epidemiology of COPD (COPDGene) study.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-7\"><jats:title>Exposures<\/jats:title><jats:p>Modified Lung Function Questionnaire (mLFQ) scores and COPD PRS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcome was spirometry-defined moderate to severe COPD (forced expiratory volume in the first second of expiration\/forced vital capacity [FEV<jats:sub>1<\/jats:sub>\/FVC] &amp;amp;lt;0.7 and FEV<jats:sub>1<\/jats:sub> [percent predicted] &amp;amp;lt;80%). The performance of logistic models was assessed using the PRS, mLFQ score, and PRS plus mLFQ score for predicting spirometry-defined COPD.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-9\"><jats:title>Results<\/jats:title><jats:p>Among 3385 FHS participants (median age, 52.0 years; 45.9% male) and 4095 COPDGene participants (median age, 56.8 years; 55.5% male) who reported no history of COPD, 160 (4.7%) FHS and 775 (18.9%) COPDGene participants had spirometry-defined COPD. Adding the PRS to the mLFQ score significantly improved the area under the curve from 0.78 to 0.84 (<jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) in FHS, 0.69 to 0.72 (<jats:italic>P<\/jats:italic>\u2009=\u2009.04) in COPDGene non-Hispanic African American, and 0.75 to 0.78 (<jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) in COPDGene non-Hispanic White participants. At a risk threshold for spirometry referral of 10%, the addition of the PRS to the mLFQ score correctly reclassified 13.8% (95% CI, 6.6%-21.0%) of COPD cases in FHS, but not in COPDGene.<\/jats:p><\/jats:sec><jats:sec id=\"ab-joi240141-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>A COPD PRS enhances the identification of undiagnosed COPD beyond a conventional case-finding approach in the general population. Further research is needed to assess its impact on COPD diagnosis and outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2024.24212","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T16:32:54Z","timestamp":1737563574000},"page":"784","source":"Crossref","is-referenced-by-count":21,"title":["Polygenic Risk Score Added to Conventional Case Finding to Identify Undiagnosed Chronic Obstructive Pulmonary Disease"],"prefix":"10.1001","volume":"333","author":[{"given":"Jingzhou","family":"Zhang","sequence":"first","affiliation":[{"name":"The Pulmonary Center, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Section of Pulmonary, Allergy, Sleep & Critical Care Medicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, 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Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sparrow","sequence":"additional","affiliation":[{"name":"The Pulmonary Center, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Section of Pulmonary, Allergy, Sleep & Critical Care Medicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"},{"name":"Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E.","family":"Ortega","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston 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