{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:15:02Z","timestamp":1772018102013,"version":"3.50.1"},"reference-count":112,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000738","name":"VA","doi-asserted-by":"publisher","award":["Grant 5 IK2 BX 003841-02"],"award-info":[{"award-number":["Grant 5 IK2 BX 003841-02"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["Grant F30-HL140756"],"award-info":[{"award-number":["Grant F30-HL140756"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Major depressive disorder (MDD) is a common comorbidity in chronic obstructive pulmonary disease (COPD), affecting up to 57% of patients with COPD. Although the comorbidity of COPD and MDD is well established, the causal relationship between these two diseases is unclear. A large-scale electronic health record clinical biobank and genome-wide association study summary statistics for MDD and lung function traits were used to investigate potential shared underlying genetic susceptibility between COPD and MDD. Linkage disequilibrium score regression was used to estimate genetic correlation between phenotypes. Polygenic risk scores (PRS) for MDD and lung function traits were developed and used to perform a phenome-wide association study (PheWAS). Multi-trait-based conditional and joint analysis identified single-nucleotide polymorphisms (SNPs) influencing both lung function and MDD. We found genetic correlations between MDD and all lung function traits were small and not statistically significant. A PRS\u2013MDD was significantly associated with an increased risk of COPD in a PheWAS [odds ratio (OR)\u2009=\u20091.12, 95% confidence interval (CI): 1.09\u20131.16] when adjusting for age, sex and genetic ancestry, but this relationship became attenuated when controlling for smoking history (OR\u2009=\u20091.08, 95% CI: 1.04\u20131.13). No significant associations were found between the lung function PRS and MDD. Multi-trait-based conditional and joint analysis identified three SNPs that may contribute to both traits, two of which were previously associated with mood disorders and COPD. Our findings suggest that the observed relationship between COPD and MDD may not be driven by a strong shared genetic architecture.<\/jats:p>","DOI":"10.1093\/hmg\/ddab068","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T04:16:42Z","timestamp":1614745002000},"page":"619-628","source":"Crossref","is-referenced-by-count":11,"title":["Fate or coincidence: do COPD and major depression share genetic risk factors?"],"prefix":"10.1093","volume":"30","author":[{"given":"Victoria L","family":"Martucci","sequence":"first","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Richmond","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center, Nashville, TN 37212, USA"},{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea K","family":"Davis","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy S","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center, Nashville, TN 37212, USA"},{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy J","family":"Cox","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Samuels","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Digna","family":"Velez Edwards","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda C","family":"Aldrich","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"2022031004492178000_ref1","volume-title":"Global Health Estimates 2016: Disease Burden by Cause, Age, Sex, by Country and by Region, 2000-2016","author":"World Health Organization","year":"2018"},{"key":"2022031004492178000_ref2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1055\/s-0035-1556063","article-title":"Comorbidities and chronic obstructive pulmonary disease: prevalence, influence on outcomes, and management","volume":"36","author":"Putcha","year":"2015","journal-title":"Semin. 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