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Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

No convincing association between genetic markers and respiratory symptoms: results of a GWA study

Authors: Xiang Zeng, Judith M. Vonk, Kim de Jong, Xijin Xu, Xia Huo, H. Marike Boezen

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Respiratory symptoms are associated with accelerated lung function decline, and increased hospitalization and mortality rates in the general population. Although several environmental risk factors for respiratory symptoms are known, knowledge on genetic risk factors is lacking. We aim to identify genetic variants associated with respiratory symptoms by genome-wide association (GWA) analyses.

Methods

We conducted the first GWA study on cough, dyspnea and phlegm among 7,976 participants in the LifeLines I cohort and used the LifeLines II cohort (n = 5,260) and the Vlagtwedde-Vlaardingen cohort (n = 1,529) for replication.

Results

We identified 50 SNPs that were assessed for replication. Rs16918212, located in the alpha-2-macroglobulin pseudogene 1 (A2MP1), was associated with cough in both the identification (odds ratio (OR) = 0.72, p = 5.41 × 10−5) and the meta-analyzed replication cohorts (OR = 0.83, p = 0.033). No other significant replicated associations were found.

Conclusions

Given that only 1 out of 50 SNPs showed significant replication (i.e. 2%) we conclude that we did not find a convincing association between genetic markers and respiratory symptoms. Since, environmental exposures are important risk factors for respiratory symptoms, the next step is to perform a genome-wide interaction (GWI) study to identify genetic susceptibility loci for respiratory symptoms in interaction with known harmful environmental exposures.
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Literature
1.
Jakeways N, McKeever T, Lewis SA, Weiss ST, Britton J. Relationship between FEV1 reduction and respiratory symptoms in the general population. Eur Respir J. 2003;21:658–63.CrossRefPubMed
2.
Sunyer J, Basagana X, Roca J, Urrutia I, Jaen A, Anto JM, Burney P. Relations between respiratory symptoms and spirometric values in young adults: the European community respiratory health study. Respir Med. 2004;98:1025–33.CrossRefPubMed
3.
Frostad A, Soyseth V, Andersen A, Gulsvik A. Respiratory symptoms as predictors of all-cause mortality in an urban community: a 30-year follow-up. J Intern Med. 2006;259:520–9.CrossRefPubMed
4.
Leivseth L, Nilsen TI, Mai XM, Johnsen R, Langhammer A. Lung function and respiratory symptoms in association with mortality: The HUNT Study. COPD. 2014;11:59–80.CrossRefPubMed
5.
Figarska SM, Boezen HM, Vonk JM. Dyspnea severity, changes in dyspnea status and mortality in the general population: the Vlagtwedde/Vlaardingen study. Eur J Epidemiol. 2012;27:867–76.CrossRefPubMedPubMedCentral
6.
Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med. 1996;153:1530–5.CrossRefPubMed
7.
Sherman CB, Xu X, Speizer FE, Ferris BJ, Weiss ST, Dockery DW. Longitudinal lung function decline in subjects with respiratory symptoms. Am Rev Respir Dis. 1992;146:855–9.CrossRefPubMed
8.
Sistek D, Wickens K, Amstrong R, D’Souza W, Town I, Crane J. Predictive value of respiratory symptoms and bronchial hyperresponsiveness to diagnose asthma in New Zealand. Respir Med. 2006;100:2107–11.CrossRefPubMed
9.
Jaakkola MS, Jaakkola JJ, Becklake MR, Ernst P. Effect of passive smoking on the development of respiratory symptoms in young adults: an 8-year longitudinal study. J Clin Epidemiol. 1996;49:581–6.CrossRefPubMed
10.
Elberling J, Linneberg A, Mosbech H, Dirksen A, Menne T, Nielsen NH, Madsen F, Frolund L, Johansen JD. Airborne chemicals cause respiratory symptoms in individuals with contact allergy. Contact Dermatitis. 2005;52:65–72.CrossRefPubMed
11.
Smit LA, Heederik D, Doekes G, Blom C, van Zweden I, Wouters IM. Exposure-response analysis of allergy and respiratory symptoms in endotoxin-exposed adults. Eur Respir J. 2008;31:1241–8.CrossRefPubMed
12.
Stern G, Latzin P, Roosli M, Fuchs O, Proietti E, Kuehni C, Frey U. A prospective study of the impact of air pollution on respiratory symptoms and infections in infants. Am J Respir Crit Care Med. 2013;187:1341–8.CrossRefPubMed
13.
Li S, Williams G, Jalaludin B, Baker P. Panel studies of air pollution on children’s lung function and respiratory symptoms: a literature review. J Asthma. 2012;49:895–910.CrossRefPubMed
14.
Zhang LX, Enarson DA, He GX, Li B, Chan-Yeung M. Occupational and environmental risk factors for respiratory symptoms in rural Beijing. China Eur Respir J. 2002;20:1525–31.CrossRefPubMed
15.
Marchetti N, Garshick E, Kinney GL, McKenzie A, Stinson D, Lutz SM, Lynch DA, Criner GJ, Silverman EK, Crapo JD. Association between occupational exposure and lung function, respiratory symptoms, and high-resolution computed tomography imaging in COPDGene. Am J Respir Crit Care Med. 2014;190:756–62.CrossRefPubMedPubMedCentral
16.
Chang AB, Gibson PG, Ardill J, McGarvey LP. Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough. Eur Respir J. 2007;30:66–72.CrossRefPubMed
17.
Cho HJ, Kim SH, Kim JH, Choi H, Son JK, Hur GY, Park HS. Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers. Ann Allergy Asthma Immunol. 2011;107:57–64.CrossRefPubMed
18.
Dijkstra AE, Boezen HM, van den Berge M, Vonk JM, Hiemstra PS, Barr RG, Burkart KM, Manichaikul A, Pottinger TD, Silverman EK, et al. Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD. Eur Respir J. 2015;45:60–75.CrossRefPubMed
19.
de Jong K, Vonk JM, Timens W, Bosse Y, Sin DD, Hao K, Kromhout H, Vermeulen R, Postma DS, Boezen HM. Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels. J Allergy Clin Immunol. 2015;136:1664–1672.e14.CrossRefPubMed
20.
Scholtens S, Smidt N, Swertz MA, Bakker SJ, Dotinga A, Vonk JM, van Dijk F, van Zon SK, Wijmenga C, Wolffenbuttel BH, et al. Cohort Profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44:1172–80.CrossRefPubMed
21.
de Jong K, Boezen HM, Kromhout H, Vermeulen R, Postma DS, Vonk JM. Association of occupational pesticide exposure with accelerated longitudinal decline in lung function. Am J Epidemiol. 2014;179:1323–30.CrossRefPubMed
22.
van Diemen CC, Postma DS, Vonk JM, Bruinenberg M, Schouten JP, Boezen HM. A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population. Am J Respir Crit Care Med. 2005;172:329–33.CrossRefPubMed
23.
Burney PG, Luczynska C, Chinn S, Jarvis D. The European Community Respiratory Health Survey. Eur Respir J. 1994;75:954–60.CrossRef
24.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.CrossRefPubMedPubMedCentral
25.
Blacker D, Wilcox MA, Laird NM, Rodes L, Horvath SM, Go RC, Perry R, Watson BJ, Bassett SS, McInnis MG, et al. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet. 1998;19:357–60.CrossRefPubMed
26.
Chan WL, Chang JG. Pseudogene-derived endogenous siRNAs and their function. Methods Mol Biol. 2014;1167:227–39.CrossRefPubMed
27.
Boezen HM. Genome-wide association studies: what do they teach us about asthma and chronic obstructive pulmonary disease? Proc Am Thorac Soc. 2009;6:701–3.CrossRefPubMed
28.
Goldsobel AB, Chipps BE. Cough in the pediatric population. J Pediatr. 2010;1563:352–8.CrossRef
29.
Metadata
Title
No convincing association between genetic markers and respiratory symptoms: results of a GWA study
Authors
Xiang Zeng
Judith M. Vonk
Kim de Jong
Xijin Xu
Xia Huo
H. Marike Boezen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-016-0495-4

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