Grant Number:
Principal Investigator:
Neophytou, Andreas
Institution:
University of California, Berkeley
Most Recent Award Year:
2017
Lifestage of Participants:
Exposure:
Youth (1-18 years, specifically 6-18 years of age); Adulthood (18+ years, specifically 18-23 years of age)
Assessment:
Youth (1-18 years, specifically 6-18 years of age); Adulthood (18+ years, specifically 18-23 years of age)
Exposures:
Air Pollutants:
Nitric oxide/nitrogen dioxide (NO/NO2); Ozone; Particulate matter (PM 2.5); Polycyclic aromatic hydrocarbons (PAHs); Traffic pollutants
Health Outcomes:
Immune Outcomes:
Inflammation
Metabolic Outcomes:
Metabolic syndrome; Glucose dysregulation
Other:
Oxidative stress
Respiratory Outcomes:
Airway inflammation; Asthma; Pulmonary function
Biological Sample:
Blood; Saliva/buccal cells; Urine
Other Participant Data:
Questionnaire Data, HbA1c levels; Regulatory T-cell function, 8-isoprostane (biomarker of oxidative stress); CRP (biomarker of systemic inflammation), leptin, adiponectin, and high-density lipoprotein (biomarkers of abnormal fat and glucose metabolism); Socioeconomic factors (neighborhood poverty, individual level income, parental educaiton); Genetic ancestry
Genes or Other DNA Products Studied:
Forkhead box P3 (FOXP3); Treg cell levels; Inflammatory cytokines
Epigenetic Mechanisms Studied:
Epigenetic modifications that suppress FOXP3 expression
Abstract:
Exposure to air pollution is an established risk factor for asthma, reduced lung function as well as inflammatory and oxidative processes which are in turn linked with obesity and diabetes. Risk for these adverse outcomes begins early in childhood and well-documented racial/ethnic differences and social disparities render minority children especially vulnerable, yet these populations are underrepresented in the literature. Analysis for truly representative effect estimates should consider a wide array of genetic, social and environmental factors, biologic pathways from exposure to disease, with consideration for causal mediators and interactions. Mediation and interaction analysis can also aid in determining the transportability of estimated effects from one population to another. However, estimation and interpretability of target parameters in mediation analysis is complicated by issues such as mediator-outcome interactions, non-linearities, and exposure-induced confounding, which cannot be addressed using traditional regression approaches. My long-term career goals are to assess optimal interventions on environmental health risk factors that best reduce overall risk in populations of interest. I will utilize advanced epidemiologic methods maximinzing internal validity and efficiency of estimation of target. I will expand on existing methods for estimation of effects in the presence of time varying exposures and covariates as well as exposure-induced mediator outcome confounding (estimation of controlled direct effects and the randomized intervention analogues for the natural direct and indirect effects) which cannot be addressed with traditional regression approaches. The proposed methodology will be suitable for assessment of potential interventions on continuous exposures, which will be especially beneficial in the area of environmental epidemiology. In Aims 1 & 2 of this proposal I will use these proposed methods to assess direct, indirect and total effects of air pollution exposures on risk of asthma, overall lung function and metabolic syndrome, within a counterfactual framework. I am well suited to perform the proposed research based on 1) my past experience in environmental health and advanced methods and counterfactual approaches 2) the exceprional interdisciplinary mentoring team I have assembled and 3) the unique research opportunity offered by the datasets in the proposal, comprised largely of minority children. This proposed study will enable me to quantify mediated effects of air pollution exposures in especially vulnerable populations. I will be advised by a world-class team of mentors to expand my expertise in integrating advanced epidemiologic methods with causal inference applications (e.g., machine learning and efficient estimators of causal inference parameters) in environmental epidemiological studies; epigenetic and exposomic factors as potential modifiers or mediators of effect; and health disparities and social factors associated with environmental exposures. The proposed research and training will enable me to establish an independent career as a leader in intervention assessment and causal inference in environmental epidemiology
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Related NIEHS-Funded Study Populations
Children's Health and Air Pollution Study (CHAPS)
Principal Investigator:
Hammond, Katharine; Balmes, John; Nadeau, Kari; Shaw, Gary
| Study Population Page Study Population c31
Institution:
University of California, Berkeley and Stanford University
Location:
San Joaquin Valley, California
Number of Participants::
~625
Brief Description::
This prospective study examines how exposure to air pollution influences allergic and metabolic disease risk in children and young adults. The study has enrolled over 600 participants living in the San Joaquin Valley region in central California.
Genes-Environments & Admixture in Studies of Latino Americans (GALA I and II)
Principal Investigator:
Burchard, Esteban Gonzalez
| Study Population Page Study Population c58
Institution:
University of California, San Francisco
Location:
Mexico City, Mexico (GALA I) San Francisco, California (GALA I & II); Denver, Colorado (GALA II); Chicago, Illinois (GALA II); New York, New York (GALA I & II); Puerto Rico (GALA I & II); Houston, Texas (GALA II)
Number of Participants::
~7,000 GALA I and II participants
Brief Description::
The GALA studies investigate how genetic and environmental risk factors interact to influence asthma and asthma-related traits among Latino ethnic groups with diverse ancestry. With more than 7,000 participants, the GALA studies make up the largest pediatric asthma genetic study of Latino populations in the U.S. Participants were 8-21 years old at the time of enrollment. The GALA studies include two study populations: 1) the Genetics of Asthma in Latino Americans (GALA I), a family-based study examining children with asthma and their parents; and 2) the Genes-environments and Admixture in Latino Americans (GALA II), a case-control study comparing children with asthma to healthy controls. GALA I was funded by the National Heart, Lung, and Blood Institute; GALA II was funded by NIEHS.