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

Abstract

BackgroundRespiratory 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.MethodsWe 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.ResultsWe 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.ConclusionsGiven 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0495-4) contains supplementary material, which is available to authorized users.

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

“…Genome-wide association studies (GWASs) have highlighted pathways underlying a range of respiratory traits and diseases, and highlighted potentially relevant drug targets [ 12 , 13 ]. Previous GWASs of sputum production [ 14 – 17 ] have not identified any genome-wide significant findings.…”

mRNA and long non-coding RNA expression profiles of rotator cuff tear patients reveal inflammatory features in long head of biceps tendon

“…Among those differentiation expressed lncRNAs, several thoroughly studied molecules including A2MP1, C1QTNF1-AS1, CASC2, FTCDNL1, FTX, LOC339975 and TWIST1, which expressed in other diseases, were also significantly changed in LHBT. 50 SNPs were identified and evaluated for replication by Zeng et al Through genome-wide association analysis, Rs16918212 located in A2MP1 was associated with cough in both the identification odds ratio and the meta-analyzed replication cohort [ 32 ]. Li et al showed that C1QTNF1-AS1, who firstly down-regulated miR-221-3p and then up-regulated SOCS3, can inhibit the proliferation, migration and invasion of human liver cancer cells, and further accelerate apoptosis by acting on the JAK/STAT signaling pathway [ 33 ].…”

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

“…We sought replication in five general population cohorts which surveyed participants for chronic sputum production; Generation Scotland [25], EXCEED Study [26], LifeLines 1, LifeLines 2 and Vlagtwedde-Vlaardingen [17]. Further details are provided in the Supplementary text.…”

“…Genome-wide association studies have highlighted pathways underlying a range of respiratory traits and diseases, and highlighted potentially relevant drug targets [16, 17]. Previous genome wide association studies of sputum production have been limited to cohorts of smokers [18, 19] or those with diagnosed COPD [20, 21] and have not identified any genome-wide significant findings.…”