Abstract

The etiology of sex differences in the risk of asthma-COPD phenotype and COPD is still not completely understood. Genetic and environmental risk factors are commonly believed to play an important role. This study aims to identify sex-specific genetic markers associated with asthma-COPD phenotype and COPD using the Canadian Longitudinal Study on Aging (CLSA) Baseline Comprehensive and Genomic data. There were a total of 1,415 COPD cases. Out of them, 504 asthma-COPD phenotype cases were identified. 20,524 participants without a diagnosis of asthma and COPD served as controls. We performed genome-wide SNP-by-sex interaction analysis. SNPs with an interaction p-value < 10⁻⁵ were included in a sex-stratified multivariable logistic regression for asthma-COPD phenotype and COPD outcomes. 18 and 28 SNPs had a significant interaction term p-value < 10⁻⁵ with sex in the regression analyses of asthma-COPD phenotype and COPD outcomes, respectively. Sex-stratified multivariable analysis of asthma-COPD phenotype showed that 7 SNPs in/near SMYD3, FHIT, ZNF608, RIMBP2, ZNF133, BPIFB1, and S100B loci were significant in males. Sex-stratified multivariable analysis of COPD showed that 8 SNPs in/near MAGI1, COX18, OSTC, ELOVL5, C7orf72 FGF14, and NKAIN4 were significant in males, and 4 SNPs in/near genes CAMTA1, SATB2, PDE10A, and LINC00908 were significant in females. An SNP in the ZPBP gene was associated with COPD in both males and females. Identification of sex-specific loci associated with asthma-COPD phenotype and COPD may offer valuable evidence toward a better understanding of the sex-specific differences in the pathophysiology of the diseases.

摘要

哮喘-慢性阻塞性肺病表型和慢性阻塞性肺病风险的性别差异的病因尚不完全清楚。人们普遍认为遗传和环境风险因素起着重要作用。本研究旨在利用加拿大老龄化纵向研究 (CLSA) 基线综合和基因组数据来确定与哮喘-慢性阻塞性肺病表型和慢性阻塞性肺病相关的性别特异性遗传标记。共有 1,415 例慢性阻塞性肺病病例。其中，确定了 504 例哮喘-慢性阻塞性肺病表型病例。20,524 名未诊断患有哮喘和慢性阻塞性肺病的参与者作为对照。我们进行了全基因组 SNP 与性别的相互作用分析。相互作用p值<10 ^-5的SNP被纳入哮喘-COPD表型和COPD结果的性别分层多变量逻辑回归中。在哮喘-COPD 表型和 COPD 结果的回归分析中，18 和 28 个 SNP 分别与性别具有显着的交互项 p 值 < 10 ^{-5 。}哮喘-COPD 表型的性别分层多变量分析显示，SMYD3、FHIT、ZNF608、RIMBP2、ZNF133、BPIFB1 和 S100B 基因座中/附近的 7 个 SNP 在男性中显着。COPD的性别分层多变量分析显示，MAGI1、COX18、OSTC、ELOVL5、C7orf72 FGF14和NKAIN4中/附近的8个SNP在男性中显着，而CAMTA1、SATB2、PDE10A和LINC00908基因中/附近的4个SNP在男性中显着。女性。ZPBP 基因中的 S​​NP 与男性和女性的 COPD 相关。鉴定与哮喘-慢性阻塞性肺病表型和慢性阻塞性肺病相关的性别特异性位点可能为更好地了解疾病病理生理学中的性别特异性差异提供有价值的证据。