Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
There is an urgent need for research to better understand the mechanisms of asthma in the obese, and to develop new therapies specifically targeted to this unique patient population.
Background: Leptin, a pro-inflammatory cytokine produced by adipose tissue, has previously been shown to be associated with asthma in children. We hypothesised that high serum leptin concentrations would also be associated with asthma in adults. Methods: The Third National Health and Nutrition Examination Survey is a cross sectional study that included fasting serum leptin concentrations and self-report of doctor diagnosed asthma. Data were analysed using multivariable logistic regression analysis. Results: Of 5876 participants, those with current asthma had a higher mean unadjusted leptin concentration than those who had never had asthma (geometric mean (SE) 9.2 (0.6) mg/l v 7.6 (0.2) mg/l; p = 0.02). After adjustment for triceps skinfold thickness and other covariates, the association between leptin and asthma appeared stronger in women than in men, and in premenopausal women than in postmenopausal women. Body mass index (BMI) was also associated with current asthma in women, but this association was not significantly affected by adjustment for leptin concentrations. Conclusions:The results of this large population based study support the hypothesis that leptin is associated with asthma in women. In addition, while BMI also is related to asthma in women, this study does not support the suggestion that leptin contributes significantly to this association.
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
Background: The association of murine asthma with adiposity may be mediated by adiponectin, an antiinflammatory adipokine with reduced serum concentrations in obese subjects. A study was undertaken to examine whether the serum adiponectin concentration is associated with human asthma and whether it explains the association between adiposity and asthma, particularly in women and in premenopausal women. Methods: A cross-sectional analysis was performed of 2890 eligible subjects at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and its YALTA ancillary study who had either current asthma or never asthma at that evaluation. Obesity was defined as body mass index (BMI) >30 kg/m 2 . Multivariable logistic regression analysis was performed with current asthma status as the dependent variable. Results: Women, but not men, with current asthma had a lower mean unadjusted serum adiponectin concentration than those with never asthma (p,0.001; p for sex interaction ,0.001). Similarly, current asthma was related to obesity only in women (OR 3.31, 95% CI 2.00 to 5.46, p for sex interaction = 0.004); this association was little affected by adjusting for serum adiponectin. The prevalence of current asthma in premenopausal women was reduced in the highest compared with the lowest tertile of serum adiponectin concentration (OR 0.46, 95% CI 0.26 to 0.84, p = 0.03), after adjusting for BMI. However, the interaction between serum adiponectin concentration and BMI category on current asthma status was not significant in premenopausal women or women overall. Conclusions: A high serum adiponectin concentration may protect against current asthma in premenopausal women but does not explain the association between asthma and adiposity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.