Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults.

RATIONALE: Electronic cigarette (e-cigarette) aerosol contains volatile aldehydes, including flavourings and oxidant metals with known pulmonary toxicity. OBJECTIVES: To evaluate the associations of e-cigarette use with symptoms of wheeze, bronchitic symptoms and shortness of breath (SOB) across 4 years of prospective data. METHODS: Participants completed questionnaires on respiratory symptoms and past 30-day e-cigarette, cigarette and cannabis use in 2014 (wave 1; N=2094; mean age 17.3 years, SD=0.6 years). Follow-up information was collected in 2015 (wave 2; n=1609), 2017 (wave 3; n=1502) and 2018 (wave 4; n=1637) using online surveys. Mixed-effects logistic regression models evaluated associations of e-cigarette use with respiratory symptoms. MEASUREMENTS AND MAIN RESULTS: Participants were mostly Hispanic white (51.8%) and evenly representative by sex (49.6% female; 50.4% male). Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis. CONCLUSIONS: E-cigarette use in young adults was associated with respiratory symptoms, independent of combustible cannabis and cigarette exposures.

Inclusion of optic neuritis in dissemination in space improves the performance of McDonald 2017 criteria in Hispanic people with suspected multiple sclerosis.

BACKGROUND: Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria. OBJECTIVE: To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON. METHODS: Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria (p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70)). CONCLUSION: This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people.

Effects of dual use of e-cigarette and cannabis during adolescence on cigarette use in young adulthood.

INTRODUCTION: E-cigarette and cannabis use by adolescents are risk factors for smoking initiation. We hypothesised that increasingly common dual use of e-cigarette and cannabis in adolescence leads to more frequent cigarette smoking in young adulthood. METHODS: Data are from a prospective cohort study in Southern California, where 1164 participants who ever used nicotine products in their lifetime completed surveys in 12th grade (T1:2016), and at 24-month (T2) and 42-month (T3) follow-ups. Past 30-day use (number of days: range=0-30) of cigarettes, e-cigarettes and cannabis, and nicotine dependence, were assessed in each survey. Nicotine dependence for cigarettes and e-cigarettes was assessed using original and modified (for e-cigarette) Hooked on Nicotine Checklists (number of dependent products: range=0-2). Path analysis examined the mediation process via nicotine dependence linking baseline e-cigarette and cannabis use to subsequent increased cigarette use. RESULTS: Baseline exclusive use of e-cigarettes (baseline prevalence, 2.5%) was associated with 2.61-fold increase in frequency of smoking days at T3 (95% CI 1.04 to 13.1), exclusive cannabis use (26.0%) with 2.58-fold increase (95% CI 1.43 to 4.98), and dual use (7.4%) with 5.84-fold increase (95% CI 3.16 to 12.81), compared with baseline non-users. Nicotine dependence at T2 mediated 10.5% (95% CI 6.3 to 14.7) and 23.2% (95% CI 9.6 to 36.3) of the association of cannabis and dual use, respectively, with increased smoking at T3. DISCUSSION: Adolescent e-cigarette and cannabis use was associated with more frequent smoking during young adulthood, with larger effects of dual use. Associations were partially mediated through nicotine dependence. Dual use of cannabis and e-cigarettes may contribute to the development of nicotine dependence and increased use of combustible cigarettes.

Secondhand nicotine vaping at home and respiratory symptoms in young adults.

RATIONALE: Despite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure. OBJECTIVE: To investigate whether exposure to secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults. METHOD: We investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders. RESULTS: Prevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders. CONCLUSION: Secondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.

Association of Changes in Air Quality With Incident Asthma in Children in California, 1993-2014.

Importance: Exposure to air pollutants is a well-established cause of asthma exacerbation in children; whether air pollutants play a role in the development of childhood asthma, however, remains uncertain. Objective: To examine whether decreasing regional air pollutants were associated with reduced incidence of childhood asthma. Design, Setting, and Participants: A multilevel longitudinal cohort drawn from 3 waves of the Southern California Children's Health Study over a period of air pollution decline. Each cohort was followed up from 4th to 12th grade (8 years): 1993-2001, 1996-2004, and 2006-2014. Final follow-up for these data was June 2014. Population-based recruitment was from public elementary schools. A total of 4140 children with no history of asthma and residing in 1 of 9 Children's Health Study communities at baseline were included. Exposures: Annual mean community-level ozone, nitrogen dioxide, and particulate matter less than 10 µm (PM10) and less than 2.5 µm (PM2.5) in the baseline year for each of 3 cohorts. Main Outcomes and Measures: Prospectively identified incident asthma, collected via questionnaires during follow-up. Results: Among the 4140 children included in this study (mean [SD] age at baseline, 9.5 [0.6] years; 52.6% female [n = 2 179]; 58.6% white [n = 2273]; and 42.2% Hispanic [n = 1686]), 525 incident asthma cases were identified. For nitrogen dioxide, the incidence rate ratio (IRR) for asthma was 0.80 (95% CI, 0.71-0.90) for a median reduction of 4.3 parts per billion, with an absolute incidence rate decrease of 0.83 cases per 100 person-years. For PM2.5, the IRR was 0.81 (95% CI, 0.67-0.98) for a median reduction of 8.1 µg/m3, with an absolute incidence rate decrease of 1.53 cases per 100 person-years. For ozone, the IRR for asthma was 0.85 (95% CI, 0.71-1.02) for a median reduction of 8.9 parts per billion, with an absolute incidence rate decrease of 0.78 cases per 100 person-years. For PM10, the IRR was 0.93 (95% CI, 0.82-1.07) for a median reduction of 4.0 µg/m3, with an absolute incidence rate decrease of 0.46 cases per 100 person-years. Conclusions and Relevance: Among children in Southern California, decreases in ambient nitrogen dioxide and PM2.5 between 1993 and 2014 were significantly associated with lower asthma incidence. There were no statistically significant associations for ozone or PM10.

Genetic ancestry influences asthma susceptibility and lung function among Latinos.

BACKGROUND: Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. OBJECTIVE: To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. METHODS: We analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. RESULTS: Native American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively). CONCLUSION: Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos.

Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants.

BACKGROUND: Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. OBJECTIVES: To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Children's Health Study. METHODS: Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO2), nitric oxide (NO) and total nitrogen oxides (NOx). Exposure to regional ozone (O3), NO2, particulate matter with aerodynamic diameter <10 µm (PM10) and 2.5 µm (PM2.5) was measured continuously at community monitors. RESULTS: An increase in near-roadway NOx of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV1) (p=0.048). Effects were observed in all communities and were similar for NO2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2-3% were associated with regional PM10 and PM2.5 (FVC and FEV1) and with O3 (FEV1), but not NO2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. CONCLUSIONS: The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function.

Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis.

BACKGROUND: Biologically plausible mechanisms link traffic-related air pollution to metabolic disorders and potentially to obesity. Here we sought to determine whether traffic density and traffic-related air pollution were positively associated with growth in body mass index (BMI = kg/m2) in children aged 5-11 years. METHODS: Participants were drawn from a prospective cohort of children who lived in 13 communities across Southern California (N = 4550). Children were enrolled while attending kindergarten and first grade and followed for 4 years, with height and weight measured annually. Dispersion models were used to estimate exposure to traffic-related air pollution. Multilevel models were used to estimate and test traffic density and traffic pollution related to BMI growth. Data were collected between 2002-2010 and analyzed in 2011-12. RESULTS: Traffic pollution was positively associated with growth in BMI and was robust to adjustment for many confounders. The effect size in the adjusted model indicated about a 13.6% increase in annual BMI growth when comparing the lowest to the highest tenth percentile of air pollution exposure, which resulted in an increase of nearly 0.4 BMI units on attained BMI at age 10. Traffic density also had a positive association with BMI growth, but this effect was less robust in multivariate models. CONCLUSIONS: Traffic pollution was positively associated with growth in BMI in children aged 5-11 years. Traffic pollution may be controlled via emission restrictions; changes in land use that promote jobs-housing balance and use of public transit and hence reduce vehicle miles traveled; promotion of zero emissions vehicles; transit and car-sharing programs; or by limiting high pollution traffic, such as diesel trucks, from residential areas or places where children play outdoors, such as schools and parks. These measures may have beneficial effects in terms of reduced obesity formation in children.

Childhood air pollutant exposure and carotid artery intima-media thickness in young adults.

BACKGROUND: Exposure to ambient air pollutants increases risk for cardiovascular health outcomes in adults. The contribution of childhood air pollutant exposure to cardiovascular health has not been thoroughly evaluated. METHODS AND RESULTS: The Testing Responses on Youth study consists of 861 college students recruited from the University of Southern California in 2007 to 2009. Participants attended 1 study visit during which blood pressure, heart rate, and carotid artery intima-media thickness (CIMT) were assessed. Self-administered questionnaires collected information about health and sociodemographic characteristics, and a 12-hour fasting blood sample was drawn for lipid and biomarker analyses. Residential addresses were geocoded and used to assign cumulative air pollutant exposure estimates based on data derived from the U.S. Environmental Protection Agency's Air Quality System database. The associations between CIMT and air pollutants were assessed using linear regression analysis. Mean CIMT was 603 µm (±54 SD). A 2 standard deviation (SD) increase in childhood (aged 0-5 years) or elementary school (aged 6-12 years) O(3) exposure was associated with a 7.8-µm (95% confidence interval, -0.3-15.9) or 10.1-µm (95% confidence interval, 1.8-18.5) higher CIMT, respectively. Lifetime exposure to O(3) showed similar but nonsignificant associations. No associations were observed for PM(2.5), PM(10), or NO(2), although adjustment for these pollutants strengthened the childhood O(3) associations. CONCLUSIONS: Childhood exposure to O(3) may be a novel risk factor for CIMT in a healthy population of college students. Regulation of air pollutants and efforts that focus on limiting childhood exposures continue to be important public health goals.

Disparities in greenspace associated with sleep duration among adolescent children in Southern California.

More than half of adolescent children do not get the recommended 8 hours of sleep necessary for optimal growth and development. In adults, several studies have evaluated effects of urban stressors including lack of greenspace, air pollution, noise, nighttime light, and psychosocial stress on sleep duration. Little is known about these effects in adolescents, however, it is known that these exposures vary by socioeconomic status (SES). We evaluated the association between several environmental exposures and sleep in adolescent children in Southern California. Methods: In 2010, a total of 1476 Southern California Children's Health Study (CHS) participants in grades 9 and 10 (mean age, 13.4 years; SD, 0.6) completed a questionnaire including topics on sleep and psychosocial stress. Exposures to greenspace, artificial light at night (ALAN), nighttime noise, and air pollution were estimated at each child's residential address, and SES was characterized by maternal education. Odds ratios and 95% confidence intervals (95% CIs) for sleep outcomes were estimated by environmental exposure, adjusting for age, sex, race/ethnicity, home secondhand smoke, and SES. Results: An interquartile range (IQR) increase in greenspace decreased the odds of not sleeping at least 8 hours (odds ratio [OR], 0.86 [95% CI, 0.71, 1.05]). This association was significantly protective in low SES participants (OR, 0.77 [95% CI, 0.60, 0.98]) but not for those with high SES (OR, 1.16 [95%CI, 0.80, 1.70]), interaction P = 0.03. Stress mediated 18.4% of the association among low SES participants. Conclusions: Residing in urban neighborhoods of greater greenness was associated with improved sleep duration among children of low SES but not higher SES. These findings support the importance of widely reported disparities in exposure and access to greenspace in socioeconomically disadvantaged populations.

Assessing household fine particulate matter (PM2.5) through measurement and modeling in the Bangladesh cook stove pregnancy cohort study (CSPCS).

Biomass fuel burning is a significant contributor of household fine particulate matter (PM2.5) in the low to middle income countries (LMIC) and assessing PM2.5 levels is essential to investigate exposure-related health effects such as pregnancy outcomes and acute lower respiratory infection in infants. However, measuring household PM2.5 requires significant investments of labor, resources, and time, which limits the ability to conduct health effects studies. It is therefore imperative to leverage lower-cost measurement techniques to develop exposure models coupled with survey information about housing characteristics. Between April 2017 and March 2018, we continuously sampled PM2.5 in three seasonal waves for approximately 48-h (range 46 to 52-h) in 74 rural and semi-urban households among the participants of the Bangladesh Cook Stove Pregnancy Cohort Study (CSPCS). Measurements were taken simultaneously in the kitchen, bedroom, and open space within the household. Structured questionnaires captured household-level information related to the sources of air pollution. With data from two waves, we fit multivariate mixed effect models to estimate 24-h average, cooking time average, daytime and nighttime average PM2.5 in each of the household locations. Households using biomass cookstoves had significantly higher PM2.5 concentrations than those using electricity/liquefied petroleum gas (626 µg/m3 vs. 213 µg/m3). Exposure model performances showed 10-fold cross validated R2 ranging from 0.52 to 0.76 with excellent agreement in independent tests against measured PM2.5 from the third wave of monitoring and ambient PM2.5 from a separate satellite-based model (correlation coefficient, r = 0.82). Significant predictors of household PM2.5 included ambient PM2.5, season, and types of fuel used for cooking. This study demonstrates that we can predict household PM2.5 with moderate to high confidence using ambient PM2.5 and household characteristics. Our results present a framework for estimating household PM2.5 exposures in LMICs, which are often understudied and underrepresented due to resource limitations.

Cohort profile: Bangladesh Cook Stove Pregnancy Cohort Study (CSPCS).

PURPOSE: The Cook Stove Pregnancy Cohort Study (CSPCS) was designed to assess the effects of biomass fuel use on household air pollution (HAP) as well as the effects of HAP (fine particulate matter, PM2.5) on birth outcomes and acute lower respiratory infection (ALRI) among infants in Bangladesh. PARTICIPANTS: We recruited 903 women within 18 weeks of pregnancy from rural and semiurban areas of Bangladesh between November 2016 and March 2017. All women and their infants (N=831 pairs) were followed until 12 months after delivery and a subset have undergone respiratory and gut microbiota analysis. METHODS: Questionnaires were administered to collect detailed sociodemographic, medical, nutritional and behavioural information on the mother-child dyads. Anthropometric measurements and biological samples were also collected, as well as household PM2.5 concentrations. FINDINGS TO DATE: Published work in this cohort showed detrimental effects of biomass fuel and health inequity on birth outcomes. Current analysis indicates high levels of household PM2.5 being associated with cooking fuel type and infant ALRI. Lastly, we identified distinct gut and respiratory microbial communities at 6 months of age. FUTURE PLANS: This study provides an economical yet effective framework to conduct pregnancy cohort studies determining the health effects of adverse environmental exposures in low-resource countries. Future analyses in this cohort include assessing the effect of indoor PM2.5 levels on (1) physical growth, (2) neurodevelopment, (3) age of first incidence and frequency of ALRI in infants and (4) the development of the respiratory and gut microbiome. Additional support has allowed us to investigate the effect of in utero exposure to metals on infant neurodevelopment in the first year of life.

Parental stress increases the detrimental effect of traffic exposure on children's lung function.

RATIONALE: Emerging evidence indicates that psychosocial stress enhances the effect of traffic exposure on the development of asthma. OBJECTIVES: We hypothesized that psychosocial stress would also modify the effect of traffic exposure on lung function deficits. METHODS: We studied 1,399 participants in the Southern California Children's Health Study undergoing lung function testing (mean age, 11.2 yr). We used hierarchical mixed models to assess the joint effect of traffic-related air pollution and stress on lung function. MEASUREMENTS AND MAIN RESULTS: Psychosocial stress in each child's household was assessed based on parental response to the perceived stress scale (range, 0-16) at study entry. Exposures to nitric oxide, nitrogen dioxide, and total oxides of nitrogen (NOx), surrogates of the traffic-related pollution mixture, were estimated at schools and residences based on a land-use regression model. Among children from high-stress households (parental perceived stress scale > 4) deficits in FEV1 of 4.5 (95% confidence interval, -6.5 to -2.4) and of 2.8% (-5.7 to 0.3) were associated with each 21.8 ppb increase in NOx at homes and schools, respectively. These pollutant effects were significantly larger in the high-stress compared with lower-stress households (interaction P value 0.007 and 0.05 for residential and school NOx, respectively). No significant NOx effects were observed in children from low-stress households. A similar pattern of association was observed for FVC. The observed associations for FEV1 and FVC remained after adjusting for sociodemographic factors and after restricting the analysis to children who do not have asthma. CONCLUSIONS: A high-stress home environment is associated with increased susceptibility to lung function effects of air pollution both at home and at school.

Providing Solution in an Emergency: COVID-19 and Voice Behavior of Healthcare Professionals.

This study investigates the mechanism between idiosyncratic deals (I-deals) and voice behavior, considering display aggression and deontic justice as mediating variables. We collected data from 702 nurses and their immediate supervisors who work with COVID-19 patients through survey questionnaires at two different times, and we analyzed the data using structural equation modeling (SEM). We found that I-deals are significantly associated with deontic justice and voice behavior. Moreover, I-deals are significant but negatively associated with displayed aggression, which is significant and negatively associated with voice behavior. In addition, deontic justice and display aggression mediate the association between I-deals and voice behavior. These findings suggest that the hospitals' top management should provide I-deals to nurses to improve their voice behavior.

Social inequality influences the impact of household air pollution on birth outcomes.

BACKGROUND: Studies demonstrated associations between maternal exposure to household air pollution from cooking and increased risk of adverse birth outcomes in offspring; however, the modifying effect of socioeconomic status (SES) on this association has not been explored. OBJECTIVES: In a cohort of pregnant women with 800 single live births between 2016 and 2017 in rural and semi urban areas of Bangladesh, we tested the hypotheses that kitchen location and cooking fuel type affect birth outcomes (birth weight, low birth weight [LBW] and small for gestational age [SGA]) and these associations vary by SES. METHODS: Demographic characteristics including SES, kitchen location and fuel type were assessed in prenatal visits. Neonatal anthropometric measurements were recorded within 72 h of births. We performed multivariable linear and logistic regressions adjusting for potential confounders to test the study hypotheses. RESULTS: For newborns from households with indoor kitchens, adjusted mean birth weight was 65.13 g (95% confidence interval [CI]: -118.37, -11.90) lower and the odds of LBW and SGA were 58% (odds ratio [OR]:1.58, 95% CI: 1.12, 2.24) and 41% (OR: 1.41, 95% CI: 1.05, 1.92) higher compared to those born in households with outdoor kitchens. We found SES significantly modified the associations between kitchen location and birth outcomes in households using biomass fuels. Newborns from low SES households with indoor kitchens had 89 g lower birth weight and a higher odds of being born with LBW (OR: 2.08, 95% CI 1.23, 3.58), and SGA (OR: 1.70, 95% CI 1.06, 2.76) than those born in high SES households using outdoor kitchens. CONCLUSIONS: In areas with poor access or affordability to clean fuel such as in our study population, cooking in an outdoor kitchen can reduce the burden of LBW and SGA, particularly for low SES households. Promoting outdoor kitchens is a possible intervention strategy to mitigate adverse birth outcomes.

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.

Role of inducible nitric oxide synthase in asthma risk and lung function growth during adolescence.

BACKGROUND: Inducible nitric oxide (NO) synthase (iNOS, encoded by NOS2A) produces NO in response to environmental stimuli, which can result in nitrosative stress. Because nitrosative stress affects respiratory health, it was hypothesised that variants in NOS2A are associated with asthma incidence and lung function growth during adolescence. METHODS: In this prospective study, spirometric testing was performed at school and a presence or absence of asthma was ascertained annually by questionnaire among children participating in the Southern California Children's Health Study. 24 single nucleotide polymorphisms (SNPs) of the NOS2A region (with seven promoter SNPs in one haplotype block), spanning 20 kb upstream and 10 kb downstream were genotyped. Association between the NOS2A region and asthma or lung function growth was tested using genetic block-specific principal component and haplotype analyses. This study was restricted to children with Latino and Caucasian ancestry for analyses of both asthma (n=1596) and lung function growth (n=2108). RESULT: A pair of "yin-yang" haplotypes in the promoter region showed strong association with new-onset asthma and lung function growth. The "yin" haplotype (h0111101) was associated with 44% increased asthma risk (p=0.003) and reduced forced expiratory volume in 1 s (FEV(1)) growth from 10 to 18 years of age (-29.46 ml, p=0.07), whereas the "yang"(h1000010) haplotype was associated with 23% reduced asthma risk (p=0.13) and better FEV(1) growth (43.84 ml, p=0.01). Furthermore, the increased asthma risk associated with h0111101 was restricted to children with the GSTM1 "null" genotype (interaction p=0.002, HR 1.89, 95% CI 1.34 to 2.60). CONCLUSION: Common haplotypes in the NOS2A promoter are associated with new-onset asthma and lung function growth. These effects are stronger in adolescents with the GSTM1 "null" genotype.

Variation in the GST mu locus and tobacco smoke exposure as determinants of childhood lung function.

RATIONALE: The glutathione S-transferases (GSTs) are important detoxification enzymes. OBJECTIVES: To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure. METHODS: In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts. For each child, tagging single nucleotide polymorphisms in GSTM2, GSTM3, GSTM4, and GSTM5 loci were genotyped. Using principal components and haplotype analyses, the significance of each locus in relation to level and growth of FEV1, maximum midexpiratory flow rate (MMEF), and FVC was evaluated. Interactions between loci and tobacco smoke on lung function were also investigated. MEASUREMENTS AND MAIN RESULTS: Variation in the GST mu family locus was associated with lower FEV1 (P = 0.01) and MMEF (0.04). Two haplotypes of GSTM2 were associated with FEV1 and MMEF, with effect estimates in opposite directions. One haplotype in GSTM3 showed a decrease in growth for MMEF (-164.9 ml/s) compared with individuals with other haplotypes. One haplotype in GSTM4 showed significantly decreased growth in FEV1 (-51.3 ml), MMEF (-69.1 ml/s), and FVC (-44.4 ml), compared with all other haplotypes. These results were consistent across two independent cohorts. Variation in GSTM2 was particularly important for FVC and FEV(1) among children whose mothers smoked during pregnancy. CONCLUSIONS: Genetic variation across the GST mu locus is associated with 8-year lung function growth. Children of mothers who smoked during pregnancy and had variation in GSTM2 had lower lung function growth.

Roles of arginase variants, atopy, and ozone in childhood asthma.

BACKGROUND: Arginases (encoded by ARG1 and ARG2 genes) might play an important role in asthma pathogenesis through effects on nitrosative stress. Arginase expression is upregulated in asthma and varies with T(H)2 cytokine levels and oxidative stress. OBJECTIVE: We aimed to examine whether variants in these genes are associated with asthma and whether atopy and exposures to smoking and air pollution influence the associations. METHODS: Among non-Hispanic and Hispanic white participants of the Children's Health Study (n = 2946), we characterized variation in each locus (including promoter region) with 6 tag single nucleotide polymorphisms for ARG1 and 10 for ARG2. Asthma was defined by parental report of physician-diagnosed asthma at study entry. RESULTS: Both ARG1 and ARG2 genetic loci were significantly associated with asthma (global locus level P = .02 and .04, respectively). Compared with the most common haplotype within each locus, 1 ARG1 haplotype was associated with reduced risk (odds ratio [OR] per haplotype copy, 0.55; 95% CI, 0.36-0.84), and 1 ARG2 haplotype was associated with increased risk (OR per haplotype copy, 1.35; 95% CI, 1.04-1.76) of asthma. The effect of the ARG1 haplotype that was significantly associated with asthma varied by the child's history of atopy and ambient ozone (P(interaction) = .04 and .02, respectively). Among atopic children living in high-ozone communities, those carrying the ARG1 haplotype had reduced asthma risk (OR per haplotype copy, 0.12; 95% CI, 0.04-0.43; P(heterogeneity) across atopy/ozone categories = .008). CONCLUSIONS: ARG1 and ARG2 loci are associated with childhood asthma. The association between ARG1 variation and asthma might depend on atopy and ambient ozone levels.

Role of Family Motivation, Workplace Civility and Self-Efficacy in Developing Affective Commitment and Organizational Citizenship Behavior.

The mechanism connecting the antecedents to positive attitudes like affective commitment (AC) and positive behaviors like organizational citizenship behavior (OCB) is an under-researched area in the field of positive organizational scholarship. Drawing on Social Exchange Theory (SET), this study empirically validates family motivation and civility as antecedents of affective commitment and organizational citizenship behavior through the mediating mechanism of self-efficacy. The process by Hayes (2013) was used to analyze time-lagged and multi-source data collected from 335 employees of educational and telecom sector. Results indicate that the relationship of affective commitment with family motivation and civility is partially mediated whereas the relationship of organizational citizenship behavior with family motivation and civility is fully mediated by self-efficacy. This study adds to the literature of family-work enrichment accounts by validating family motivation as a novel antecedent for positive behavioral outcomes. The implications of the study are discussed.