RT期刊文章SR电子T1小说轨迹for exertional dyspnoea in childhood asthma JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2001224 DO 10.1183/13993003.01224-2020 VO 57 IS 2 A1 Lee, Sanghun A1 Lasky-Su, Jessica Ann A1 Lange, Christoph A1 Kim, Wonji A1 Kumar, Preeti Lakshman A1 McDonald, Merry-Lynn N. A1 Vaz Fragoso, Carlos A. A1 Laurie, Cecelia A1 Raby, Benjamin A. A1 , A1 Celedón, Juan C. A1 Cho, Michael H. A1 Won, Sungho A1 Weiss, Scott T. A1 Hecker, Julian YR 2021 UL //www.qdcxjkg.com/content/57/2/2001224.abstract AB Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma.Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study.In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10−9) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10−10). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 (ACKR3).Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies.WGS data from a family-based association study suggest that the replicated SNP variant rs10165869 is associated with exertional dyspnoea, likely through the expression of ACKR3 https://bit.ly/3a5ddBd