ORCID Profile
0000-0002-4890-4012
Current Organisation
University of Bristol
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Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 16-07-2018
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
DOI: 10.1038/S41588-018-0197-6
Abstract: In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2017
Publisher: American Thoracic Society
Date: 07-2019
Publisher: Elsevier BV
Date: 07-2014
Publisher: Public Library of Science (PLoS)
Date: 30-06-2020
Publisher: European Respiratory Society (ERS)
Date: 29-09-2021
DOI: 10.1183/23120541.00457-2021
Abstract: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts. We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, –15, –20, –25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV 1 /FVC z-score ≥LLN, and FVC z-score LLN. The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m −2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46). Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.ENVINT.2020.105749
Abstract: Residing in greener areas is increasingly linked to beneficial health outcomes, but little is known about its effect on respiratory health. We examined associations between residential greenness and nearby green spaces with lung function up to 24 years in the UK Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Lung function was measured by spirometry at eight, 15 and 24 years of age. Greenness levels within circular buffers (100-1000 m) around the birth, eight-, 15- and 24-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index and averaged (lifetime greenness). The presence and proportion of green spaces (urban green spaces, forests and agricultural land) within a 300 m buffer was determined. First, associations between repeated greenness and green space variables and repeated lung function parameters were assessed using generalized estimation equations (N = 7094, 47.9% male). Second, associations between lifetime average greenness and lifetime average proportion of green spaces with lung function at 24-years were assessed using linear regression models (N = 1763, 39.6% male). All models were adjusted for in idual and environmental covariates. Using repeated greenspace and lung function data at eight, 15 and 24 years, greenness in a 100 m buffer was associated with higher FEV This study provides suggestive evidence that children whose homes are in more vegetated places or are in close proximity of green spaces have better lung function up to 24 years of age.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2021
DOI: 10.1186/S12890-021-01611-6
Abstract: Observational studies show an association between reduced lung function and impaired cognition. Cognitive dysfunction influences important health outcomes and is a precursor to dementia, but treatments options are currently very limited. Attention has therefore focused on identifying modifiable risk factors to prevent cognitive decline and preserve cognition. Our objective was to determine if lung function or risk of COPD causes reduced cognitive function using Mendelian randomization (MR). Single nucleotide polymorphisms from genome wide association studies of lung function and COPD were used as exposures. We examined their effect on general cognitive function in a s le of 132,452 in iduals. We then performed multivariable MR (MVMR), examining the effect of lung function before and after conditioning for covariates. We found only weak evidence that reduced lung function (Beta − 0.002 (SE 0.02), p -value 0.86) or increased liability to COPD (− 0.008 (0.008), p -value 0.35) causes lower cognitive function. MVMR found both reduced FEV 1 and FVC do cause lower cognitive function, but that after conditioning for height (− 0.03 (0.03), p -value 0.29 and − 0.01 (0.03) p -value 0.62, for FEV1 and FVC respectively) and educational attainment (− 0.03 (0.03) p -value 0.33 and − 0.01 (0.02), p -value 0.35) the evidence became weak. We did not find evidence that reduced lung function or COPD causes reduced cognitive function. Previous observational studies are probably affected by residual confounding. Research efforts should focus on shared risk factors for reduced lung function and cognition, rather than lung function alone as a modifiable risk factor.
Publisher: American Thoracic Society
Date: 15-04-2022
Publisher: Springer Science and Business Media LLC
Date: 11-08-2016
Publisher: Wiley
Date: 06-2022
DOI: 10.1111/PAI.13802
Abstract: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi‐ancestry meta‐analysis of genome‐wide association studies (meta‐GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across erse populations and to assess their functional role in regulating DNA methylation and gene expression. A meta‐GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants ( p ≤ 5 × 10 −5 ) were assessed for replication in 36,477 European and 1078 non‐European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. One hundred and twenty‐six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule‐1/exostosin like glycosyltransferase‐2 ( VCAM1 / EXTL2 ) (discovery: odds ratio (OR T allele ) = 0.82, p = 9.05 × 10 −6 and replication: OR T allele = 0.89, p = 5.35 × 10 −3 ) and rs943126 from pantothenate kinase 1 ( PANK1 ) (discovery: OR C allele = 0.85, p = 3.10 × 10 −5 and replication: OR C allele = 0.89, p = 1.30 × 10 −2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. This multi‐ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.
Publisher: Springer Science and Business Media LLC
Date: 16-03-2023
DOI: 10.1186/S12931-023-02383-9
Abstract: Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence. In the Avon Longitudinal Study of Parents and Children, ‘processed’, ‘traditional’, and ‘health-conscious’ dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC (FEF 25–75 ) were measured at 15.5 years and were transformed to z-scores based on the Global Lung Function Initiative curves. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years. In multivariable-adjusted models, the ‘health-conscious’ pattern was positively associated with FEV 1 (regression coefficient comparing top versus bottom quartile of pattern score 0.16, 95% CI 0.01 to 0.31, P for trend 0.04) and FVC (0.18, 95% CI 0.04 to 0.33, P for trend 0.02), while the ‘processed’ pattern was negatively associated with FVC (− 0.17, 95% CI − 0.33 to − 0.01, P for trend 0.03). Associations between the ‘health-conscious’ and ‘processed’ patterns and lung function were modified by SCGB1A1 and GPX4 gene polymorphisms. We found no evidence of an association between the ‘traditional’ pattern and lung function, nor between any pattern and FEF 25–75 or incident asthma. A ‘health-conscious’ diet in mid-childhood was associated with higher subsequent lung function, while a diet high in processed food was associated with lower lung function.
Publisher: Springer Science and Business Media LLC
Date: 03-2019
Publisher: Public Library of Science (PLoS)
Date: 07-2014
Publisher: Elsevier BV
Date: 08-2012
Publisher: F1000 Research Ltd
Date: 24-05-2021
DOI: 10.12688/WELLCOMEOPENRES.15846.2
Abstract: Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent in iduals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P x10 -8 ) interactions with sex on lung function, and 21 showed suggestive interactions (P x10 -6 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1 ) (P=3.15x10 -15 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP ) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6 ), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Raquel Granell.