Zeng Xiang, Vonk Judith M, de Jong Kim, Xu Xijin, Huo Xia, Boezen H Marike
Department of Epidemiology, University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.
Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.
Respir Res. 2017 Jan 10;18(1):11. doi: 10.1186/s12931-016-0495-4.
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.
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.
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) and the meta-analyzed replication cohorts (OR = 0.83, p = 0.033). No other significant replicated associations were found.
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.
呼吸道症状与肺功能加速下降、普通人群住院率和死亡率增加有关。尽管已知几种呼吸道症状的环境风险因素，但缺乏关于遗传风险因素的知识。我们旨在通过全基因组关联（GWA）分析确定与呼吸道症状相关的基因变异。
我们对生命线I队列中的7976名参与者进行了首次关于咳嗽、呼吸困难和咳痰的GWA研究，并使用生命线II队列（n = 5260）和弗拉格特韦德-弗拉尔丁根队列（n = 1529）进行重复验证。
我们鉴定了50个单核苷酸多态性（SNP）进行重复验证。位于α-2-巨球蛋白假基因1（A2MP1）中的Rs16918212在鉴定队列（优势比（OR）= 0.72，p = 5.41×10）和荟萃分析的重复验证队列（OR = 0.83，p = 0.033）中均与咳嗽相关。未发现其他显著的重复关联。
鉴于50个SNP中只有1个显示出显著的重复验证（即2%），我们得出结论，未发现遗传标记与呼吸道症状之间有令人信服的关联。由于环境暴露是呼吸道症状的重要风险因素，下一步是进行全基因组相互作用（GWI）研究，以确定与已知有害环境暴露相互作用的呼吸道症状遗传易感性位点。
