Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function
| Autor: | Bernd Meibohm, Nadia N. Hansel, Medea Imboden, Susan R. Heckbert, Stephen B. Kritchevsky, Henry Völzke, María Soler Artigas, Jerome I. Rotter, Ivan Curjuric, Daan W. Loth, Albert Hofman, Guy Brusselle, Vilmundur Gudnason, R. Graham Barr, George T. O'Connor, Matthew Kowgier, Thomas Lumley, Jemma B. Wilk, J Hansen, Tamara B. Harris, Stefan Karrasch, Bruno H. Stricker, Wei Gao, Alan James, Xiangjun Gu, David P. Strachan, Martin D. Tobin, Joachim Heinrich, Myriam Fornage, Yongmei Liu, Gail Davies, Alanna C. Morrison, Akshay Sood, Lyle J. Palmer, Alexander Teumer, Millennia Foy, Bill Musk, Holger Schulz, Patricia A. Cassano, Guo Li, O. Dale Williams, Lenore J. Launer, Michael Allerhand, Bruce M. Psaty, Melinda C. Aldrich, Lars Lind, Fernando Rivadeneira, David Couper, Kurt Lohman, Sven Gläser, Emily Hodge, Bonnie R. Joubert, Rasika A. Mathias, John M. Starr, Lies Lahousse, Tove Fall, Kathleen C. Barnes, Erik Ingelsson, Stephanie J. London, Ian J. Deary, Martin T. Wells, Kari E. North, Ashok Kumar, Arend Voorman, Eva Albrecht, Wendy L. McArdle, Albert V. Smith, Ingo Ruczinski, Beate Koch, Josée Dupuis, Nicole Probst-Hensch, Nora Franceschini, Lewis J. Smith, Dana B. Hancock, Wenbo Tang, Ian P. Hall, Sina A. Gharib, Louise V. Wain, Andrew P. Morris, André G. Uitterlinden, Cecilia M. Lindgren |
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| Přispěvatelé: | Chen, Lin, Otorhinolaryngology and Head and Neck Surgery, Epidemiology, Public Health, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Candidate gene Pulmonology Epidemiology Respiratory Medicine and Allergy Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology) Molecular Biology Microbiology Biochemistry or Biopharmacy) lcsh:Medicine Genome-wide association study 0302 clinical medicine Medicine and Health Sciences MALIC ENZYME Longitudinal Studies Pair 11 lcsh:Science Lung Lungmedicin och allergi Genetics 0303 health sciences education.field_of_study Multidisciplinary Respiration Genomics Genetic Epidemiology Respiratory Female Human Research Article EXPRESSION Adult medicine.medical_specialty FUNCTION DECLINE General Science & Technology Chronic Obstructive Pulmonary Disease Population Locus (genetics) Biology OBSTRUCTIVE PULMONARY-DISEASE Chromosomes 03 medical and health sciences Chromosome 15 Clinical Research Molecular genetics medicine Humans education Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi) molekylärbiologi mikrobiologi biokemi eller biofarmaci) 030304 developmental biology Genetic association INTERLEUKIN-16 Prevention HEARING-LOSS Chromosomes Human Pair 11 Human Genome lcsh:R GLOBAL BURDEN GENE respiratory tract diseases 030228 respiratory system Genetic epidemiology Gene Expression Regulation Genetic Loci FOS: Biological sciences ASTHMA lcsh:Q Gene expression Lungs EPIDERMODYSPLASIA-VERRUCIFORMIS Genome-Wide Association Study |
| Zdroj: | PLoS ONE, Vol 9, Iss 7, p e100776 (2014) PLoS ONE PLOS ONE PloS one, vol 9, iss 7 Tang, W, Kowgier, M, Loth, D W, Soler Artigas, M, Joubert, B R, Hodge, E, Gharib, S A, Smith, A V, Ruczinski, I, Gudnason, V, Mathias, R A, Harris, T B, Hansel, N N, Launer, L J, Barnes, K C, Hansen, J G, Albrecht, E, Aldrich, M C, Allerhand, M, Barr, R G, Brusselle, G G, Couper, D J, Curjuric, I, Davies, G, Deary, I J, Dupuis, J, Fall, T, Foy, M, Franceschini, N, Gao, W, Gläser, S, Gu, X, Hancock, D B, Heinrich, J, Hofman, A, Imboden, M, Ingelsson, E, James, A, Karrasch, S, Koch, B, Kritchevsky, S B, Kumar, A, Lahousse, L, Li, G, Lind, L, Lindgren, C, Liu, Y, Lohman, K, Lumley, T, McArdle, W L, Meibohm, B, Morris, A P, Morrison, A C, Musk, B, North, K E, Palmer, L J, Probst-Hensch, N M, Psaty, B M, Rivadeneira, F, Rotter, J I, Schulz, H, Smith, L J, Sood, A, Starr, J M, Strachan, D P, Teumer, A, Uitterlinden, A G, Völzke, H, Voorman, A, Wain, L V, Wells, M T, Wilk, J B, Williams, O D, Heckbert, S R, Stricker, B H, London, S J, Fornage, M, Hall, I P & Cassano, P A 2014, ' Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function ', PLoS ONE, vol. 9, no. 7, pp. e100776 . https://doi.org/10.1371/journal.pone.0100776 PLoS One (print), 9(7). Public Library of Science |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. |
| Databáze: | OpenAIRE |
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