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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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16\u00d710<jats:sup>\u22129<\/jats:sup>) 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\u00d710<jats:sup>\u221210<\/jats:sup>). 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 (<jats:italic>ACKR3<\/jats:italic>).<\/jats:p><jats:p>Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases\/studies.<\/jats:p>","DOI":"10.1183\/13993003.01224-2020","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T17:20:25Z","timestamp":1598548825000},"page":"2001224","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel locus for exertional dyspnoea in childhood asthma"],"prefix":"10.1183","volume":"57","author":[{"given":"Sanghun","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica 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