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      Sex-Specific Genetic Determinants of Asthma-COPD Phenotype and COPD in Middle-Aged and Older Canadian Adults: An Analysis of CLSA Data.

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          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.

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          Author and article information

          Journal
          COPD
          COPD
          Informa UK Limited
          1541-2563
          1541-2563
          Dec 2023
          : 20
          : 1
          Affiliations
          [1 ] Clinical Epidemiology Unit, Division of Community Health and Humanities, Faculty of Medicine, Memorial University, St. John's, Canada.
          [2 ] School of Public Health, University of Alberta, Edmonton, Canada.
          [3 ] Faculty of Medicine, Health Sciences Centre (Respirology Department), Memorial University, St John's, Newfoundland and Labrador, Canada.
          Article
          10.1080/15412555.2023.2229906
          37466093
          27a2631a-718a-4b3e-88ea-7d5699ac00e3
          History

          CLSA,chronic obstructive pulmonary disease,polymorphisms,sex,Asthma-COPD phenotype

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