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BackgroundAirflow obstruction is a hallmark of chronic obstructive pulmonary disease (COPD), and is defined as either the ratio between forced expiratory volume in one second and forced vital capacity (FEV1/FVC) MethodsGWASes were performed in the LifeLines Cohort Study for both airflow obstruction definitions in never-smokers (NS = 5071) and ever-smokers (ES = 4855). The FEV1/FVC 1/FVC - 4 were validated in the Vlagtwedde-Vlaardingen and Rotterdam Study cohorts (NS = 1966, ES = 3134) and analysed for expression quantitative trait loci (eQTL) in lung tissue (n = 1087).ResultsIn the LifeLines cohort, 96% and 93% of the never- and ever-smokers were classified concordantly based on the two definitions. 26 and 29% of the investigated SNPs were overlapping at p - 4 the overlap was 4% and 6% respectively, which could be change findings as shown by simulation studies. The effect estimates of the SNPs of the two definitions correlated strongly, but the p-values showed more variation and correlated only moderately. Similar observations were made in the Vlagtwedde-Vlaardingen study. Two overlapping SNPs in never-smokers (NFYC and FABP7) had the same direction of effect in the validation cohorts and the NFYC SNP was an eQTL for NFYC-AS1. NFYC is a transcription factor that binds to several known COPD genes, and FABP7 may be involved in abnormal pulmonary development.ConclusionsThe definition of airflow obstruction and the population under study may be important determinants of which SNPs are associated with airflow obstruction. The genes FABP7 and NFYC(-AS1) could play a role in airflow obstruction in never-smokers specifically.

Original publication

DOI

10.1186/s12890-019-0811-0

Type

Journal article

Journal

BMC pulmonary medicine

Publication Date

07/03/2019

Volume

19

Addresses

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands.

Keywords

Lung, Humans, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, CCAAT-Binding Factor, Tumor Suppressor Proteins, Vital Capacity, Forced Expiratory Volume, Spirometry, Linear Models, Logistic Models, Cohort Studies, Smoking, Polymorphism, Single Nucleotide, Genes, Overlapping, Quantitative Trait Loci, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, Fatty Acid-Binding Protein 7