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BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers. METHODS: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders. RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances. CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.
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BACKGROUND: Air pollution is positively associated with some childhood cancers, whereas greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early-life air pollution and greenness exposure and childhood cancer in Texas (1995 to 2011). METHODS: We included 6101 cancer cases and 109â762 controls (aged 0 to 16 years). We linked residential birth address to census tract annual average fine particulate matter <2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests). RESULTS: Increasing residential early-life PM2.5 exposure was associated with all childhood cancers (OR = 1.10, 95% CI = 1.06 to 1.15), lymphoid leukemias (OR = 1.15, 95% CI = 1.07 to 1.23), Hodgkin lymphomas (OR = 1.27, 95% CI = 1.02 to 1.58), non-Hodgkin lymphomas (OR = 1.24, 95% CI = 1.02 to 1.51), ependymoma (OR = 1.27, 95% CI = 1.01 to 1.60), and others. Increasing NDVI exposure was inversely associated with ependymoma (0- to 4-year-old OR = 0.75, 95% CI = 0.58 to 0.97) and medulloblastoma (OR = 0.75, 95% CI = 0.62 to 0.91) but positively associated with malignant melanoma (OR = 1.75, 95% CI = 1.23 to 2.47) and Langerhans cell histiocytosis (OR = 1.56, 95% CI = 1.07 to 2.28). There was evidence of statistical interaction between NDVI and PM2.5 (P < .04) for all cancers. CONCLUSION: Increasing early-life exposure to PM2.5 increased the risk of childhood cancers. NDVI decreased the risk of 2 cancers yet increased the risk of others. These findings highlight the complexity between PM2.5 and NDVI in cancer etiology.
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Exposição Ambiental , Neoplasias , Material Particulado , Sistema de Registros , Humanos , Criança , Pré-Escolar , Texas/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Lactente , Feminino , Adolescente , Masculino , Estudos de Casos e Controles , Material Particulado/efeitos adversos , Material Particulado/análise , Exposição Ambiental/efeitos adversos , Recém-Nascido , Poluição do Ar/efeitos adversos , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS). METHODS: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C). FINDINGS: Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs. INTERPRETATION: Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases. FUNDING: Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and the Wellcome Trust.
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Abandono do Hábito de Fumar , Poluição por Fumaça de Tabaco , Adulto , Humanos , Recém-Nascido , Metilação de DNA , Epigênese Genética , Fumar/efeitos adversos , Fumar/genética , Fumar Tabaco , Ilhas de CpGRESUMO
Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.
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Risk factors for pediatric brain tumors are largely unknown. Identifying spatial clusters of these rare tumors on the basis of residential address may provide insights into childhood socio-environmental factors that increase susceptibility. From 2000-2017, the Texas Cancer Registry recorded 4305 primary brain tumors diagnosed among children (≤19 years old). We performed a spatial analysis in SaTScan to identify neighborhoods (census tracts) where the observed number of pediatric brain tumors was higher than expected. Within each census tract, the number of pediatric brain tumors was summed on the basis of residential address at diagnosis. The population estimate from the 2007-2011 American Community Survey of 0- to 19-year-olds was used as the at-risk population. p-values were calculated using Monte Carlo hypothesis testing. The age-standardized rate was 54.3 per 1,000,000. SaTScan identified twenty clusters, of which two were statistically significant (p < 0.05). Some of the clusters identified in Texas spatially implicated potential sources of environmental risk factors (e.g., proximity to petroleum production processes) to explore in future research. This work provides hypothesis-generating data for further investigations of spatially relevant risk factors of pediatric brain tumors in Texas.
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Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (PFDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.
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Metilação de DNA , Epigenoma , Recém-Nascido , Gravidez , Criança , Feminino , Humanos , Peso ao Nascer/genética , Vitamina B 12/metabolismo , Epigênese Genética , Sangue Fetal/metabolismoRESUMO
Background: Medulloblastoma, the most common malignant pediatric brain tumor, displays marked sex differences in prevalence of the four main molecular subgroups: SHH, WNT, Group 3 and Group 4. Males are more frequently diagnosed with SHH, Group 3 and 4 tumors, which have worse prognoses than WNT tumors. Little is known about sex differences in methylation profiles within subgroups. Methods: Using publicly available methylation data (Illumina HumanMethylation450K array), we compared beta values for males versus females. Differentially methylated positions (DMP) by sex within medulloblastoma subgroups were identified on the autosomes. DMPs were mapped to genes and Reactome pathway analysis was run by subgroup. Kaplan-Meier survival curves (Log-Rank p-values) were assessed for each sex within subgroup. MethylCIBERSORT was used to investigate the tumor microenvironment using deconvolution to estimate the abundances of immune cell types using DNA methylation data. Results: There were statistically significant differences in sex by medulloblastoma subgroups (chi-squared p-value=0.00004): Group 3 (n=144; 65% male), Group 4 (n=326; 67% male), SHH (n=223; 57% male) and WNT (n=70; 41% male). Females had worse survival than males for SHH (p-value=0.02). DMPs by sex were identified within subgroups: SHH (n=131), Group 4 (n=29), Group 3 (n=19), and WNT (n=16) and validated in an independent dataset. Unsupervised hierarchical clustering showed that sex-DMPs in SHH did not correlate with other tumor attributes. Ten genes with sex DMPs (RFTN1, C1orf103, FKBP1B, COL25A1, NPDC1, B3GNT1, FOXN3, RNASEH2C, TLE1, and PHF17) were shared across subgroups. Significant pathways (p<0.05) associated with DMPs were identified for SHH (n=22) and Group 4 (n=4) and included signaling pathways for RET proto-oncogene, advanced glycosylation end product receptor, regulation of KIT, neurotrophic receptors, NOTCH, and TGF-ß. In SHH, we identified DMPs in four genes (CDK6, COL25A1, MMP16, PRIM2) that encode proteins which are the target of therapies in clinical trials for other cancers. There were few sex differences in immune cell composition within tumor subgroups. Conclusion: There are sexually dimorphic methylation profiles for SHH medulloblastoma where survival differences were observed. Sex-specific therapies in medulloblastoma may impact outcomes.
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Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
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Low-cost adsorbents derived from agricultural by-products incorporated magnetic nanoparticles (NPs) are promising for wastewater treatment. They are always preferred due to their great performance and easy separation. This study reports cobalt superparamagnetic (CoFe2O4) nanoparticles (NPs) incorporated with triethanolamine (TEA) based surfactants from cashew nut shell liquid, namely TEA-CoFe2O4, for the removal of chromium (VI) ions from aqueous solutions. To have detailed characteristics of the morphology and structural properties, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometry (VSM) were employed. The fabricated TEA-CoFe2O4 particles exhibit soft and superparamagnetic properties, which make the nanoparticles easily recycled by using a magnet. Chromate adsorption on the TEA-CoFe2O4 nanomaterials reached an optimal efficiency of 84.3% at pH = 3 with the initial adsorbent dose of 10 g/L and chromium (VI) concentration of 40 mg/L. The TEA-CoFe2O4 nanoparticles can maintain the effective adsorption of chromium (VI) ion (by 29% of efficiency loss) and retain the magnetic separation using a magnet up to three cycles of the regeneration, which promise a high potential of this low-cost adsorbent for long-term treatment of heavy metal ions from polluted waters.
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Nanopartículas de Magnetita , Poluentes Químicos da Água , Cromatos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas de Magnetita/química , Adsorção , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , CinéticaRESUMO
Background: Several studies conducted in Europe have suggested a protective association between early-life farming exposures and childhood eczema or atopic dermatitis; few studies have examined associations in adults. Objectives: To investigate associations between early-life exposures and eczema among 3217 adult farmers and farm spouses (mean age 62.8 years) in a case-control study nested within an US agricultural cohort. Methods: We used sampling-weighted logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for associations between early-life exposures and self-reported doctor-diagnosed eczema (273 cases) and polytomous logistic regression to estimate ORs (95%CIs) for a 4-level outcome combining information on eczema and atopy (specific IgE≥0.35). Additionally, we explored genetic and gene-environment associations with eczema. Results: Although early-life farming exposures were not associated with eczema overall, several early-life exposures were associated with a reduced risk of having both eczema and atopy. Notably, results suggest stronger protective associations among individuals with both eczema and atopy than among those with either atopy alone or eczema alone. For example, ORs (95%CIs) for having a mother who did farm work while pregnant were 1.01 (0.60-1.69) for eczema alone and 0.80 (0.65-0.99) for atopy alone, but 0.54 (0.33-0.80) for having both eczema and atopy. A genetic risk score based on previously identified atopic dermatitis variants was strongly positively associated with eczema, and interaction testing suggested protective effects of several early-life farming exposures only in individuals at lower genetic risk. Conclusions: In utero and childhood farming exposures are associated with decreased odds of having eczema with atopy in adults.
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BACKGROUND: In low- and middle-income countries, burning biomass indoors for cooking or heating has been associated with poorer lung function. In high-income countries, wood, a form of biomass, is commonly used for heating in rural areas with increasing prevalence. However, in these settings the potential impact of chronic indoor woodsmoke exposure on pulmonary function is little studied. OBJECTIVE: We evaluated the association of residential wood burning with pulmonary function in case-control study of asthma nested within a U.S. rural cohort. METHODS: Using sample weighted multivariable linear regression, we estimated associations between some and frequent wood burning, both relative to no exposure, in relation to forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC), and fractional exhaled nitric oxide (FeNO). We examined effect modification by smoking or asthma status. RESULTS: Among all participants and within smoking groups, wood burning was not appreciably related to pulmonary function. However, in individuals with asthma (n=1,083), frequent wood burning was significantly associated with lower FEV1 [ß: -164mL; 95% confidence interval (CI): -261, -66mL], FVC (ß: -125mL; 95% CI: -230, -20mL), and FEV1/FVC (ß: -2%; 95% CI: -4, -0.4%), whereas no appreciable association was seen in individuals without asthma (n=1,732). These differences in association by asthma were statistically significant for FEV1 (pinteraction=0.0044) and FEV1/FVC (pinteraction=0.049). Frequent wood burning was also associated with higher FeNO levels in all individuals (n=2,598; ß: 0.1 ln(ppb); 95% CI: 0.02, 0.2), but associations did not differ by asthma or smoking status. DISCUSSION: Frequent exposure to residential wood burning was associated with a measure of airway inflammation (FeNO) among all individuals and with lower pulmonary function among individuals with asthma. This group may wish to reduce wood burning or consider using air filtration devices. https://doi.org/10.1289/EHP10734.
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Asma , Madeira , Asma/epidemiologia , Volume Expiratório Forçado , Humanos , Pulmão , Capacidade VitalRESUMO
Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, <0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.
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Metilação de DNA , Epigenoma , Ilhas de CpG , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , PulmãoRESUMO
BACKGROUND: Pesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides. OBJECTIVES: We conducted an EWAS of DNA methylation in relation to several pesticide active ingredients. METHODS: The Agricultural Lung Health Study is a case-control study of asthma, nested within the Agricultural Health Study. We analyzed blood DNA methylation measured using Illumina's EPIC array in 1,170 male farmers of European ancestry. For pesticides still on the market at blood collection (2009-2013), we evaluated nine active ingredients for which at least 30 participants reported past and current (within the last 12 months) use, as well as seven banned organochlorines with at least 30 participants reporting past use. We used robust linear regression to compare methylation at individual C-phosphate-G sites (CpGs) among users of a specific pesticide to never users. RESULTS: Using family-wise error rate (p<9×10-8) or false-discovery rate (FDR<0.05), we identified 162 differentially methylated CpGs across 8 of 9 currently marketed active ingredients (acetochlor, atrazine, dicamba, glyphosate, malathion, metolachlor, mesotrione, and picloram) and one banned organochlorine (heptachlor). Differentially methylated CpGs were unique to each active ingredient, and a dose-response relationship with lifetime days of use was observed for most. Significant CpGs were enriched for transcription motifs and 28% of CpGs were associated with whole blood cis-gene expression, supporting functional effects of findings. We corroborated a previously reported association between dichlorodiphenyltrichloroethane (banned in the United States in 1972) and epigenetic age acceleration. DISCUSSION: We identified differential methylation for several active ingredients in male farmers of European ancestry. These may serve as biomarkers of chronic exposure and could inform mechanisms of long-term health outcomes from pesticide exposure. https://doi.org/10.1289/EHP8928.
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Epigenoma , Praguicidas , Estudos de Casos e Controles , Metilação de DNA , Humanos , Pulmão , Masculino , Praguicidas/toxicidadeRESUMO
Solar-driven carbon dioxide (CO2) conversion has gained tremendous attention as a prominent strategy to simultaneously reduce the atmospheric CO2 concentration and convert solar energy into solar fuels in the form of chemical bonds. Numerous efforts have been devoted to diverse photo-driven processes for CO2 conversion, which utilized a multidisciplinary strategy. Among them, the architecture of nanostructured metal-based catalysts is emerging as an eminent solution for the design of catalysts of this field. In this work, we first provide fundamental mechanisms of photochemical, photoelectrochemical, photothermal, and photobio(electro)chemical CO2 reduction processes to achieve an in-deep understanding of vital aspects. Importantly, the recent progress in the catalyst design for each reaction system is discussed and highlighted. Based on these analyses, an overview of photo-driven CO2 reduction on metal-based catalysts for solar fuel production is also spotlighted. Finally, we analyze challenges and prospects for the strategic direction of developments in the field.
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Dióxido de Carbono , Energia Solar , Catálise , Metais , Luz SolarRESUMO
It is estimated that 300,000 children 0-14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high-income countries. In spite of this, the etiologies of pediatric cancer are largely unknown. Environmental exposures have long been thought to play an etiologic role. However, to date, there are few well-established environmental risk factors for pediatric malignancies, likely due to technical barriers in collecting biological samples prospectively in pediatric populations for direct measurements. In this review, we propose the use of novel or underutilized biospecimens (dried blood spots and teeth) and molecular approaches for exposure assessment (epigenetics, metabolomics, and somatic mutational profiles). Future epidemiologic studies of pediatric cancer should incorporate novel exposure assessment methodologies, data on molecular features of tumors, and a more complete assessment of gene-environment interactions.
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Metabolômica , Neoplasias , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Neoplasias/epidemiologia , Neoplasias/etiologia , Dente DecíduoRESUMO
RATIONALE: Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene-environment interactions, but studies are few. METHODS: We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case-control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV1, FVC and FEV1/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value<5×10-9) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r2=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions. RESULTS: Each trait was highly significantly associated with its GRS (all three p values<8.9×10-8). The inverse association of the GRS with FEV1/FVC was stronger for current smokers (pinteraction=0.017) or former smokers (pinteraction=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (pinteraction=0.053). No significant interactions were observed between any GRS and house dust endotoxin. CONCLUSIONS: Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma.
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Asma , Estudo de Associação Genômica Ampla , Adulto , Asma/genética , Estudos de Casos e Controles , Endotoxinas/toxicidade , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversosRESUMO
Importance: Neighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood. Objective: To evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation. Design, Setting, and Participants: This cross-sectional study used data from the Sister Study, a prospective cohort study comprising 50â¯884 women living in the US and Puerto Rico aged 35 to 74 years at enrollment who had a sister with breast cancer but had not had breast cancer themselves. Cohort enrollment occurred between July 2003 and March 2009. Participants completed a computer-assisted telephone interview on demographic, socioeconomic, lifestyle, and residential factors and provided anthropometric measures and peripheral blood samples at a home examination. DNA methylation data obtained for 2630 non-Hispanic White women selected for a case-cohort study in 2014 were used in this cross-sectional analysis. DNA methylation was measured using the HumanMethylation450 BeadChips in whole blood samples collected at baseline. Data analysis for this study was performed from October 17, 2019, to August 27, 2020. Exposures: Each participants' primary address was linked to an established index of neighborhood deprivation. Main Outcomes and Measures: Epigenetic age was estimated using 4 epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge). Age acceleration was determined using residuals from regressing chronologic age on each of the 4 epigenetic age metrics. Linear regression was used to estimate associations between neighborhood deprivation and epigenetic age acceleration as well as DNA methylation at individual cytosine-guanine sites across the genome. Results: Mean (SD) age of the 2630 participants was 56.9 (8.7) years. Those with the greatest (>75th percentile) vs least (≤25th percentile) neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum (ß = 0.23; 95% CI, 0.01-0.45), PhenoAge (ß = 0.28; 95% CI, 0.06-.50), and GrimAge (ß = 0.37; 95% CI, 0.12-0.62). Increasing US quartiles of neighborhood deprivation exhibited a trend with Hannum, PhenoAge, and GrimAge. For example, GrimAge showed a significant dose-response (P test for trend <.001) as follows: level 2 vs level 1 (ß = 0.30; 95% CI, 0.17-0.42), level 3 vs level 1 (ß = 0.35; 95% CI, 0.19-0.50), and level 4 vs level 1 (ß = 0.37; 95% CI, 0.12-0.62). Neighborhood deprivation was found to be associated with 3 cytosine-phosphate-guanine sites, with 1 of these annotated to a known gene MAOB (P = 9.71 × 10-08). Conclusions and Relevance: The findings of this study suggest that residing in a neighborhood with a higher deprivation index appears to be reflected by methylation-based markers of aging.
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Envelhecimento/genética , Metilação de DNA/genética , Epigênese Genética/genética , Características de Residência/estatística & dados numéricos , Adulto , Idoso , Antropometria/métodos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Estudos Transversais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Estudos Prospectivos , Porto Rico/epidemiologia , Fatores SocioeconômicosRESUMO
Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma; however, studies in adults are rare and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous cytosine-phosphate-guanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9×10-8, 524 at false discovery rate (FDR) less than 0.05) and implicated 382 novel genes. More CpG sites were identified in atopic asthma (181 at FWER, 1086 at FDR) and implicated 569 novel genes. 104 FDR CpG sites overlapped. 35% of CpG sites in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpG sites in non-atopic and atopic asthma. Many CpG sites from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease, as well as implicate novel genes associated with non-atopic and atopic asthma.
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Asma , Epigenoma , Adulto , Asma/genética , Estudos de Casos e Controles , Criança , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Humanos , Pulmão , Estados UnidosRESUMO
During 2015-2018, seven schools in rural Vietnam experienced diphtheria outbreaks. Multilocus sequence types were the same within schools but differed between schools. Low vaccine coverage and crowded dormitories might have contributed to the outbreaks. Authorities should consider administering routine vaccinations and booster doses for students entering the school system.