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Genome-wide association study of preserved ratio impaired spirometry (PRISm).
Higbee, Daniel H; Lirio, Alvin; Hamilton, Fergus; Granell, Raquel; Wyss, Annah B; London, Stephanie J; Bartz, Traci M; Gharib, Sina A; Cho, Michael H; Wan, Emily; Silverman, Edwin; Crapo, James D; Lominchar, Jesus V T; Hansen, Torben; Grarup, Niels; Dantoft, Thomas; Kårhus, Line; Linneberg, Allan; O'Connor, George T; Dupuis, Josée; Xu, Hanfie; De Vries, Maaike M; Hu, Xiaowei; Rich, Stephen S; Barr, R Graham; Manichaikul, Ani; Wijnant, Sara R A; Brusselle, Guy G; Lahousse, Lies; Li, Xuan; Hernández Cordero, Ana I; Obeidat, Ma'en; Sin, Don D; Harris, Sarah E; Redmond, Paul; Taylor, Adele M; Cox, Simon R; Williams, Alexander T; Shrine, Nick; John, Catherine; Guyatt, Anna L; Hall, Ian P; Davey Smith, George; Tobin, Martin D; Dodd, James W.
Afiliación
  • Higbee DH; MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
  • Lirio A; Academic Respiratory Unit, University of Bristol, Southmead Hospital, Bristol, UK.
  • Hamilton F; Department of Population Health Sciences, University of Leicester, Leicester, UK.
  • Granell R; MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
  • Wyss AB; MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
  • London SJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Bartz TM; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Gharib SA; Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, Seattle, WA, USA.
  • Cho MH; Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Wan E; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Silverman E; Harvard Medical School, Boston, MA, USA.
  • Crapo JD; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Lominchar JVT; Harvard Medical School, Boston, MA, USA.
  • Hansen T; Pulmonary and Critical Care Section, Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.
  • Grarup N; Pulmonary and Critical Care Section, Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.
  • Dantoft T; Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA.
  • Kårhus L; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Linneberg A; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • O'Connor GT; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Dupuis J; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
  • Xu H; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
  • De Vries MM; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
  • Hu X; Pulmonary Center, School of Medicine, Boston University, Boston, MA, USA.
  • Rich SS; Division of Pulmonary, Allergy, Sleep, and Critical Care Medicine, Boston Medical Center, Boston, MA, USA.
  • Barr RG; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
  • Manichaikul A; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Wijnant SRA; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Brusselle GG; Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Lahousse L; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Li X; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Hernández Cordero AI; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Obeidat M; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Sin DD; Department of Bioanalysis, Ghent University, Ghent, Belgium.
  • Harris SE; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Redmond P; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Taylor AM; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
  • Cox SR; Department of Epidemiology, Department of Respiratory Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Williams AT; Department of Bioanalysis, Ghent University, Ghent, Belgium.
  • Shrine N; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • John C; Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
  • Guyatt AL; Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
  • Hall IP; Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
  • Davey Smith G; Centre for Heart Lung Innovation, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
  • Tobin MD; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Dodd JW; Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Eur Respir J ; 63(1)2024 01.
Article en En | MEDLINE | ID: mdl-38097206
ABSTRACT

BACKGROUND:

Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities.

METHODS:

We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed.

RESULTS:

22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits.

CONCLUSION:

This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Diabetes Mellitus Tipo 2 Tipo de estudio: Systematic_reviews Límite: Humans Idioma: En Revista: Eur Respir J Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Diabetes Mellitus Tipo 2 Tipo de estudio: Systematic_reviews Límite: Humans Idioma: En Revista: Eur Respir J Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido