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Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.
Moll, Matthew; Sakornsakolpat, Phuwanat; Shrine, Nick; Hobbs, Brian D; DeMeo, Dawn L; John, Catherine; Guyatt, Anna L; McGeachie, Michael J; Gharib, Sina A; Obeidat, Ma'en; Lahousse, Lies; Wijnant, Sara R A; Brusselle, Guy; Meyers, Deborah A; Bleecker, Eugene R; Li, Xingnan; Tal-Singer, Ruth; Manichaikul, Ani; Rich, Stephen S; Won, Sungho; Kim, Woo Jin; Do, Ah Ra; Washko, George R; Barr, R Graham; Psaty, Bruce M; Bartz, Traci M; Hansel, Nadia N; Barnes, Kathleen; Hokanson, John E; Crapo, James D; Lynch, David; Bakke, Per; Gulsvik, Amund; Hall, Ian P; Wain, Louise; Weiss, Scott T; Silverman, Edwin K; Dudbridge, Frank; Tobin, Martin D; Cho, Michael H.
Afiliação
  • Moll M; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Sakornsakolpat P; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Shrine N; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
  • Hobbs BD; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • DeMeo DL; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • John C; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
  • Guyatt AL; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
  • McGeachie MJ; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Gharib SA; Computational Medicine Core, Center for Lung Biology, Department of Medicine, University of Washington, Seattle, WA, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Obeidat M; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; University of British Columbia Center for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
  • Lahousse L; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
  • Wijnant SRA; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Brusselle G; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Respiratory Medicine, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Meyers DA; Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Bleecker ER; Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Li X; Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Tal-Singer R; GlaxoSmithKline Research and Development, Collegeville, PA, USA.
  • Manichaikul A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Won S; Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, South Korea; Interdisciplinary Program of Bioinformatics, College of National Sciences, Seoul National University, Seoul, South Korea; Institute of Health and Environment, Seoul National Univers
  • Kim WJ; Department of Internal Medicine, Kangwon National University, Chuncheon, South Korea.
  • Do AR; Interdisciplinary Program of Bioinformatics, College of National Sciences, Seoul National University, Seoul, South Korea.
  • Washko GR; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Barr RG; Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
  • Psaty BM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA.
  • Bartz TM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Hansel NN; School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Barnes K; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Hokanson JE; School of Public Health, University of Colorado, Denver.
  • Crapo JD; Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, USA.
  • Lynch D; Department of Radiology, National Jewish Health, Denver, CO, USA.
  • Bakke P; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Gulsvik A; Division of Respiratory Medicine, Queen's Medical Centre, Nottingham, UK.
  • Hall IP; National Institute for Health Research Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Wain L; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Weiss ST; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Dudbridge F; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
  • Tobin MD; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK. Electronic address: martin.tobin@leicester.ac.uk.
  • Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: remhc@channing.harvard.edu.
Lancet Respir Med ; 8(7): 696-708, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649918
ABSTRACT

BACKGROUND:

Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes.

METHODS:

We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth.

FINDINGS:

The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern.

INTERPRETATION:

A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth.

FUNDING:

US National Institutes of Health, Wellcome Trust.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Agenda de Saúde Sustentável para as Américas / ODS3 - Saúde e Bem-Estar Tema em saúde: Objetivo 9: Redução de doenças não transmissíveis / Objetivo 10: Doenças transmissíveis / Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Assunto principal: Doença Pulmonar Obstrutiva Crônica Tipo de estudo: Estudo diagnóstico / Estudo de etiologia / Estudo de incidência / Estudo observacional / Patient_preference / Estudo prognóstico / Pesquisa qualitativa / Fatores de risco Aspecto: Preferência do paciente Limite: Adulto / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Lancet Respir Med Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Estados Unidos

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Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Agenda de Saúde Sustentável para as Américas / ODS3 - Saúde e Bem-Estar Tema em saúde: Objetivo 9: Redução de doenças não transmissíveis / Objetivo 10: Doenças transmissíveis / Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Assunto principal: Doença Pulmonar Obstrutiva Crônica Tipo de estudo: Estudo diagnóstico / Estudo de etiologia / Estudo de incidência / Estudo observacional / Patient_preference / Estudo prognóstico / Pesquisa qualitativa / Fatores de risco Aspecto: Preferência do paciente Limite: Adulto / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Lancet Respir Med Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Estados Unidos
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