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Gene-based analysis identified the gene ZNF248 is associated with late-onset asthma in African Americans.

ABSTRACT: Late-onset asthma (LOA) has distinct characteristics and its pathogenesis might rely on unique pathways. Although current studies are focused primarily on childhood asthma, more research is needed to show the mechanisms underlying LOA.To conduct genomewide association analysis and gene-based analysis to identify single-nucleotide polymorphisms and genes associated with LOA.The Women's Health Initiative (WHI) observational cohort and the Multi-Ethnic Study of Atherosclerosis (MESA) were used to identify subjects with LOA. The association between LOA and body mass index and smoking was evaluated. In the discovery stage of the genetic analysis, 1,218 African American subjects from WHI with genotype data (271 cases and 947 controls) were used for single-nucleotide polymorphism and gene-based association analyses. Significant or suggestive results were subsequently investigated in an independent African American population from MESA (38 cases and 806 controls).In WHI, the relative odds for LOA in obese vs normal-weight subjects was 2.55 (95% confidence interval 1.74-3.76). Ever smokers also had greater odds for LOA compared with never smokers (odds ratio 1.59, 95% confidence interval 1.21-2.09). The same trends were observed in MESA. In WHI, 6 single-nucleotide polymorphisms were associated with LOA at a genomewide-suggestive significance level (P < 1.0 × 10(-5)). The gene ZNF248 was associated with LOA and reached genomewide significance (P = 4.0 × 10(-7)). In MESA, the association between ZNF248 and LOA was successfully replicated (P = .015).Smoking and obesity are risk factors for LOA. ZNF248 confers increased susceptibility to LOA in African Americans.

SUBMITTER: Wang L

PROVIDER: S-EPMC5085297 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Gene-based analysis identified the gene ZNF248 is associated with late-onset asthma in African Americans.

Wang Leyao L Salinas Yasmmyn D YD DeWan Andrew T AT

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20160527 1

<h4>Background</h4>Late-onset asthma (LOA) has distinct characteristics and its pathogenesis might rely on unique pathways. Although current studies are focused primarily on childhood asthma, more research is needed to show the mechanisms underlying LOA.<h4>Objective</h4>To conduct genomewide association analysis and gene-based analysis to identify single-nucleotide polymorphisms and genes associated with LOA.<h4>Methods</h4>The Women's Health Initiative (WHI) observational cohort and the Multi- ...[more]

PMID: 27238579

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Project description:BackgroundLimited information exists about the nature of late-onset asthma (LOA) without medication intervention when compared to early-onset asthma (EOA). Our goal was to understand how EOA and LOA affect clinical and pathophysiological features.MethodsA population-based cross-sectional study was carried out in Zhongshan Hospital (Shanghai, China). EOA and LOA were based on age of diagnosis (before and after age 40 years, respectively). Clinical variables were collected with an emphasis on allergic features, analyzed, related, and compared using one-way ANOVA or Kruskal-Wallis test. Correlations between blood basophils and clinical data were evaluated by Spearman's rank test. Statistical analyses were conducted with SPSS v24.0.ResultsOf a total of 12,760 adults with cough, sputum, or chest tightness, 90 subjects with EOA (mean age ± standard deviation (SD):28.73 ± 5.89), 111 with LOA (mean age ± SD: 60.25 ± 9.85), and 106 with chronic obstructive pulmonary disease (COPD) (mean age ± SD: 61.58 ± 10.95) were selected. FEV1/FVC (%), FEV1% predicted, and FVC% predicted were all significantly lower in LOA compared to EOA (p < 0.01). The values of post-bronchodilator FEV1 in bronchodilator reversibility testing were higher in the LOA and EOA groups compared to subjects with COPD (p < 0.01). Among allergic features, mite sensitization was most common in EOA patients, followed by LOA and COPD, whereas mold sensitization was more prevalent in LOA than EOA. Moreover, blood eosinophils were a typical feature of asthma in both EOA and LOA compared to COPD and controls (p < 0.01), and there were no differences in blood neutrophils in LOA compared to controls. Interestingly, blood basophils were increased in both EOA (p < 0.01) and LOA (p < 0.05) compared to COPD and controls. This variable correlated with eosinophils in EOA (r = 0.549, p=0.002) but not in LOA.ConclusionLOA is a distinct clinical entity from EOA. In LOA, atopy was less frequent and spirometry values were lower when compared to EOA. In EOA, blood basophils and eosinophils were significantly correlated owing to pathophysiological differences between the two forms of the disease.

Project description:BACKGROUND:Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. The objective of the study is to identify clinically homogeneous asthma subphenotypes in a diverse sample of asthmatic children and to assess subphenotype-specific genetic ancestry in African-American asthmatic children. METHODS:A total of 1211 asthmatic children including 813 in the Childhood Asthma Management Program and 398 in the Childhood Asthma Research and Education program were studied. Unsupervised cluster analysis on clinical phenotypes was conducted to identify homogeneous subphenotypes. Subphenotype-specific genetic ancestry was estimated for 167 African-American asthmatic children. Genetic ancestry association with subphenotypes/clinical phenotypes were determined. RESULTS:Three distinct subphenotypes were identified: a moderate atopic dermatitis (AD) group with negative skin prick test (SPT) and preserved lung function; a high AD group with positive SPT and airway hyperresponsiveness; and a low AD group with positive SPT and lower lung function. African ancestry at asthma genome-wide association study (GWAS) SNPs differed between subphenotypes (64, 89, and 94% for the three subphenotypes, respectively) and was inversely correlated with AD; each additional 10% increase in African ancestry was associated with 1.5 fold higher in IgE and 6.3 higher odds of positive SPT (all p-values <?0.0001). CONCLUSIONS:By conducting phenotype-based cluster analysis and assessing subphenotype-specific genetic ancestry, we were able to identify homogeneous subphenotypes for childhood asthma that showed significant variation in genetic ancestry of African-American asthmatic children. This finding demonstrates the utility of these complementary approaches to understand and refine childhood asthma subphenotypes and enable more targeted therapy.

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Gene-based analysis identified the gene ZNF248 is associated with late-onset asthma in African Americans.

Publications

Gene-based analysis identified the gene ZNF248 is associated with late-onset asthma in African Americans.

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