Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates.
Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates.
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DOI：
10.1164/rccm.202108-1821oc
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发表时间：
2022-04-15
影响因子：
24.7
通讯作者：
Custovic, Adnan
中科院分区：
文献类型：
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作者：
Haider, Sadia;Granell, Raquel;Curtin, John;Fontanella, Sara;Cucco, Alex;Turner, Stephen;Simpson, Angela;Roberts, Graham;Murray, Clare S.;Holloway, John W.;Devereux, Graham;Cullinan, Paul;Arshad, Syed Hasan;Custovic, Adnan
当前喘息的纵向建模确定了相似的表型，但是它们的特征在研究之间常常有所不同。
我们建议，对喘息的描述可以更好地描述轨迹，而不是二进制信息的存在/不存在喘息的信息。
我们从出生到青少年的六个多维变量（包括持续时间，临时测序以及持久性/复发的程度）。肺功能和哮喘基因座的多态性17q12–21和CDHR3（与钙粘蛋白相关的家庭成员3）。
Analysis among 7,719 participants with complete data identified five spell-based wheeze phenotypes with a high degree of certainty: never (54.1%), early-transient (ETW) (23.7%), late-onset (LOW) (6.9%), persistent (PEW) (8.3%), and a novel phenotype, intermittent wheeze (INT) (6.9%). FEV1/FVC was lower in PEW and INT compared with ETW and LOW and declined from age 8 years to adulthood in INT. 17Q12–21和CDHR3多态性与较高的PEW和INT几率相关，但不是ETW或低的阶级分析和基于法术的表型，但表型内部的轨迹和表型在基于拼写的方法方面更加强大。
咒语变量的建模确定了与肺功能下降到成年早期相关的新型间歇性的表型。
Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence/absence of wheezing. We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence/recurrence). We applied partition-around-medoids clustering on these variables to derive phenotypes in five birth cohorts. We investigated within- and between-phenotype differences compared with binary latent class analysis models and ascertained associations of these phenotypes with asthma and lung function and with polymorphisms in asthma loci 17q12–21 and CDHR3 (cadherin-related family member 3). Analysis among 7,719 participants with complete data identified five spell-based wheeze phenotypes with a high degree of certainty: never (54.1%), early-transient (ETW) (23.7%), late-onset (LOW) (6.9%), persistent (PEW) (8.3%), and a novel phenotype, intermittent wheeze (INT) (6.9%). FEV1/FVC was lower in PEW and INT compared with ETW and LOW and declined from age 8 years to adulthood in INT. 17q12–21 and CDHR3 polymorphisms were associated with higher odds of PEW and INT, but not ETW or LOW. Latent class analysis- and spell-based phenotypes appeared similar, but within-phenotype individual trajectories and phenotype allocation differed substantially. The spell-based approach was much more robust in dealing with missing data, and the derived clusters were more stable and internally homogeneous. Modeling of spell variables identified a novel intermittent wheeze phenotype associated with lung function decline to early adulthood. Using multidimensional spell variables may better capture wheeze development and provide a more robust input for phenotype derivation.