TY - T1的一部小说为劳累型dyspno轨迹ea in childhood asthma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01224-2020 VL - 57 IS - 2 SP - 2001224 AU - Lee, Sanghun AU - Lasky-Su, Jessica Ann AU - Lange, Christoph AU - Kim, Wonji AU - Kumar, Preeti Lakshman AU - McDonald, Merry-Lynn N. AU - Vaz Fragoso, Carlos A. AU - Laurie, Cecelia AU - Raby, Benjamin A. AU - Celedón, Juan C. AU - Cho, Michael H. AU - Won, Sungho AU - Weiss, Scott T. AU - Hecker, Julian A2 - , Y1 - 2021/02/01 UR - //www.qdcxjkg.com/content/57/2/2001224.abstract N2 - 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 ER -