31 results on '"Boss, Jonathan"'
Search Results
2. Avocational exposure associations with ALS risk, survival, and phenotype: A Michigan-based case-control study
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Goutman, Stephen A., Boss, Jonathan, Jang, Dae Gyu, Piecuch, Caroline, Farid, Hasan, Batra, Madeleine, Mukherjee, Bhramar, Feldman, Eva L., and Batterman, Stuart A.
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- 2024
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3. Associations of self-reported occupational exposures and settings to ALS: a case–control study
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Goutman, Stephen A., Boss, Jonathan, Godwin, Christopher, Mukherjee, Bhramar, Feldman, Eva L., and Batterman, Stuart A.
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- 2022
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4. Persistent organic pollutant exposure contributes to Black/White differences in leukocyte telomere length in the National Health and Nutrition Examination Survey
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Roberts, Emily K., Boss, Jonathan, Mukherjee, Bhramar, Salerno, Stephen, Zota, Ami, and Needham, Belinda L.
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- 2022
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5. Residential exposure associations with ALS risk, survival, and phenotype: a Michigan-based case-control study.
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Goutman, Stephen A., Boss, Jonathan, Jang, Dae Gyu, Piecuch, Caroline, Farid, Hasan, Batra, Madeleine, Mukherjee, Bhramar, Feldman, Eva L., and Batterman, Stuart A.
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PROPORTIONAL hazards models , *AMYOTROPHIC lateral sclerosis , *CASE-control method , *SURVIVAL rate , *LOGISTIC regression analysis - Abstract
Environmental exposures impact amyotrophic lateral sclerosis (ALS) risk and progression, a fatal and progressive neurodegenerative disease. Better characterization of these exposures is needed to decrease disease burden. To identify exposures in the residential setting that associate with ALS risk, survival, and onset segment. ALS and control participants recruited from University of Michigan completed a survey that ascertained exposure risks in the residential setting. ALS risk was assessed using logistic regression models followed by latent profile analysis to consider exposure profiles. A case-only analysis considered the contribution of the residential exposure variables via a Cox proportional hazards model for survival outcomes and multinomial logistic regression for onset segment, a polytomous outcome. This study included 367 ALS and 255 control participants. Twelve residential variables were associated with ALS risk after correcting for multiple comparison testing, with storage in an attached garage of chemical products including gasoline or kerosene (odds ratio (OR) = 1.14, padjusted < 0.001), gasoline-powered equipment (OR = 1.16, padjusted < 0.001), and lawn care products (OR = 1.15, padjusted < 0.001) representing the top three risk factors sorted by padjusted. Latent profile analysis indicated that storage of these chemical products in both attached and detached garages increased ALS risk. Although residential variables were not associated with poorer ALS survival following multiple testing corrections, storing pesticides, lawn care products, and woodworking supplies in the home were associated with shorter ALS survival using nominal p values. No exposures were associated with ALS onset segment. Residential exposures may be important modifiable components of the ALS susceptibility and prognosis exposome. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Manganese is associated with increased plasma interleukin-1β during pregnancy, within a mixtures analysis framework of urinary trace metals
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Aung, Max T., Meeker, John D., Boss, Jonathan, Bakulski, Kelly M., Mukherjee, Bhramar, Cantonwine, David E., McElrath, Thomas F., and Ferguson, Kelly K.
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- 2020
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7. Urinary oxidative stress biomarkers and accelerated time to spontaneous delivery
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Rosen, Emma M., van ‘t Erve, Thomas J., Boss, Jonathan, Sathyanarayana, Sheela, Barrett, Emily S., Nguyen, Ruby H.N., Bush, Nicole R., Milne, Ginger L., McElrath, Thomas F., Swan, Shanna H., and Ferguson, Kelly K.
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- 2019
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8. Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort.
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Goutman, Stephen A., Boss, Jonathan, Dae-Gyu Jang, Mukherjee, Bhramar, Richardson, Rudy J., Batterman, Stuart, and Feldman, Eva L.
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PERSISTENT pollutants ,DISEASE risk factors ,TOXAPHENE ,ENVIRONMENTAL risk ,PESTICIDES ,MEDICAL personnel ,POLLUTANTS ,GENETIC risk score - Abstract
This article discusses a study published in the Journal of Neurology, Neurosurgery & Psychiatry that examines the association between persistent organic pollutants (POPs) and amyotrophic lateral sclerosis (ALS) risk and survival. The study found that higher plasma concentrations of POPs, specifically organochlorine pesticides (OCPs), were associated with greater ALS risk and shorter survival. The authors suggest that these findings support the idea that POPs may play a role in the development and progression of ALS, and that quantitative assessments of environmental pollutants could help identify individuals at risk for ALS and other neurodegenerative diseases. The article also provides information about the authors, ethical considerations, data availability, and references to other relevant studies. [Extracted from the article]
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- 2024
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9. Mediation with External Summary Statistic Information (MESSI)
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Boss, Jonathan, Hao, Wei, Cathey, Amber, Welch, Barrett M., Ferguson, Kelly K., Meeker, John D., Kang, Jian, and Mukherjee, Bhramar
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Methodology (stat.ME) ,FOS: Computer and information sciences ,Statistics - Methodology - Abstract
Environmental health studies are increasingly measuring endogenous omics data ($\boldsymbol{M}$) to study intermediary biological pathways by which an exogenous exposure ($\boldsymbol{A}$) affects a health outcome ($\boldsymbol{Y}$), given confounders ($\boldsymbol{C}$). Mediation analysis is frequently carried out to understand such mechanisms. If intermediary pathways are of interest, then there is likely literature establishing statistical and biological significance of the total effect, defined as the effect of $\boldsymbol{A}$ on $\boldsymbol{Y}$ given $\boldsymbol{C}$. For mediation models with continuous outcomes and mediators, we show that leveraging external summary-level information on the total effect improves estimation efficiency of the natural direct and indirect effects. Moreover, the efficiency gain depends on the asymptotic partial $R^2$ between the outcome ($\boldsymbol{Y}\mid\boldsymbol{M},\boldsymbol{A},\boldsymbol{C}$) and total effect ($\boldsymbol{Y}\mid\boldsymbol{A},\boldsymbol{C}$) models, with smaller (larger) values benefiting direct (indirect) effect estimation. We robustify our estimation procedure to incongenial external information by assuming the total effect follows a random distribution. This framework allows shrinkage towards the external information if the total effects in the internal and external populations agree. We illustrate our methodology using data from the Puerto Rico Testsite for Exploring Contamination Threats, where Cytochrome p450 metabolites are hypothesized to mediate the effect of phthalate exposure on gestational age at delivery. External information on the total effect comes from a recently published pooled analysis of 16 studies. The proposed framework blends mediation analysis with emerging data integration techniques., 32 pages, 6 figures
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- 2023
10. Estimating Outcome-Exposure Associations when Exposure Biomarker Detection Limits vary Across Batches
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Boss, Jonathan, Mukherjee, Bhramar, Ferguson, Kelly K., Aker, Amira, Alshawabkeh, Akram N., Cordero, José F., Meeker, John D., and Kim, Sehee
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- 2019
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11. Occupational history associates with ALS survival and onset segment.
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Goutman, Stephen A., Boss, Jonathan, Godwin, Christopher, Mukherjee, Bhramar, Feldman, Eva L., and Batterman, Stuart A.
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AMYOTROPHIC lateral sclerosis , *PROPORTIONAL hazards models , *OCCUPATIONAL exposure , *GROUNDS maintenance , *OCCUPATIONAL mortality - Abstract
To identify associations between occupational settings and self-reported occupational exposures on amyotrophic lateral sclerosis (ALS) survival and phenotypes. All patients seen in the University of Michigan Pranger ALS Clinic were invited to complete an exposure assessment querying past occupations and exposures. Standard occupational classification (SOC) codes for each job and the severity of various exposure types were derived. Cox proportional hazards models associated all-cause mortality with occupational settings and the self-reported exposures after adjusting for sex, diagnosis age, revised El Escorial criteria, onset segment, revised ALS Functional Rating Scale (ALSFRS-R), and time from symptom onset to diagnosis. Multinomial logistic regression models with three categories, adjusted for age, assessed the association between occupational settings and exposures to onset segment. Among the 378 ALS participants (median age, 64.7 years; 54.4% male), poorer survival was associated with work in SOC code "Production Occupations" and marginally with work in "Military Occupation"; poor survival associated with self-reported occupational pesticide exposure in adjusted models. Among onset segments: cervical onset was associated with ALS participants having ever worked in "Buildings and Grounds Cleaning and Maintenance Occupations," "Construction and Extraction Occupations," and "Production Occupations"; bulbar onset with self-reported occupational exposure to radiation; and cervical onset with exposure to particulate matter, volatile organic compounds, metals, combustion and diesel exhaust, electromagnetic radiation, and radiation. Occupational settings and self-reported exposures influence ALS survival and onset segment. Further studies are needed to explore and understand these relationships, most advantageously using prospective cohorts and detailed ALS registries. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Associations between mixtures of urinary phthalate metabolites with gestational age at delivery: a time to event analysis using summative phthalate risk scores
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Boss, Jonathan, Zhai, Jingyi, Aung, Max T., Ferguson, Kelly K., Johns, Lauren E., McElrath, Thomas F., Meeker, John D., and Mukherjee, Bhramar
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- 2018
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13. Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles.
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Goutman, Stephen A., Boss, Jonathan, Iyer, Gayatri, Habra, Hani, Savelieff, Masha G., Karnovsky, Alla, Mukherjee, Bhramar, and Feldman, Eva L.
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Introduction/Aims: Body mass index (BMI) is linked to amyotrophic lateral sclerosis (ALS) risk and prognosis, but additional research is needed. The aim of this study was to identify whether and when historical changes in BMI occurred in ALS participants, how these longer term trajectories associated with survival, and whether metabolomic profiles provided insight into potential mechanisms. Methods: ALS and control participants self‐reported body height and weight 10 (reference) and 5 years earlier, and at study entry (diagnosis for ALS participants). Generalized estimating equations evaluated differences in BMI trajectories between cases and controls. ALS survival was evaluated by BMI trajectory group using accelerated failure time models. BMI trajectories and survival associations were explored using published metabolomic profiling and correlation networks. Results: Ten‐year BMI trends differed between ALS and controls, with BMI loss in the 5 years before diagnosis despite BMI gains 10 to 5 years beforehand in both groups. An overall 10‐year drop in BMI associated with a 27.1% decrease in ALS survival (P =.010). Metabolomic networks in ALS participants showed dysregulation in sphingomyelin, bile acid, and plasmalogen subpathways. Discussion: ALS participants lost weight in the 5‐year period before enrollment. BMI trajectories had three distinct groups and the group with significant weight loss in the past 10 years had the worst survival. Participants with a high BMI and increase in weight in the 10 years before symptom onset also had shorter survival. Certain metabolomics profiles were associated with the BMI trajectories. Replicating these findings in prospective cohorts is warranted. See Editorial on pages 191‐192 in this issue [ABSTRACT FROM AUTHOR]
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- 2023
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14. Variable Selection with Multiply-Imputed Datasets: Choosing Between Stacked and Grouped Methods.
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Du, Jiacong, Boss, Jonathan, Han, Peisong, Beesley, Lauren J., Kleinsasser, Michael, Goutman, Stephen A., Batterman, Stuart, Feldman, Eva L., and Mukherjee, Bhramar
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POLLUTANTS , *MISSING data (Statistics) , *MATHEMATICAL optimization - Abstract
Penalized regression methods are used in many biomedical applications for variable selection and simultaneous coefficient estimation. However, missing data complicates the implementation of these methods, particularly when missingness is handled using multiple imputation. Applying a variable selection algorithm on each imputed dataset will likely lead to different sets of selected predictors. This article considers a general class of penalized objective functions which, by construction, force selection of the same variables across imputed datasets. By pooling objective functions across imputations, optimization is then performed jointly over all imputed datasets rather than separately for each dataset. We consider two objective function formulations that exist in the literature, which we will refer to as "stacked" and "grouped" objective functions. Building on existing work, we (i) derive and implement efficient cyclic coordinate descent and majorization-minimization optimization algorithms for continuous and binary outcome data, (ii) incorporate adaptive shrinkage penalties, (iii) compare these methods through simulation, and (iv) develop an R package miselect. Simulations demonstrate that the "stacked" approaches are more computationally efficient and have better estimation and selection properties. We apply these methods to data from the University of Michigan ALS Patients Biorepository aiming to identify the association between environmental pollutants and ALS risk. for this article are available online. [ABSTRACT FROM AUTHOR]
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- 2022
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15. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma
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Spagnuolo, Paul A., Hu, Jiayi, Hurren, Rose, Wang, Xiaoming, Gronda, Marcela, Sukhai, Mahadeo A., Di Meo, Ashley, Boss, Jonathan, Ashali, Iman, Beheshti Zavareh, Reza, Fine, Noah, Simpson, Craig D., Sharmeen, Sumaiya, Rottapel, Rob, and Schimmer, Aaron D.
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- 2010
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16. Group Inverse-Gamma Gamma Shrinkage for Sparse Regression with Block-Correlated Predictors
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Boss, Jonathan, Datta, Jyotishka, Wang, Xin, Park, Sung Kyun, Kang, Jian, and Mukherjee, Bhramar
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Methodology (stat.ME) ,FOS: Computer and information sciences ,Statistics - Methodology - Abstract
Heavy-tailed continuous shrinkage priors, such as the horseshoe prior, are widely used for sparse estimation problems. However, there is limited work extending these priors to predictors with grouping structures. Of particular interest in this article, is regression coefficient estimation where pockets of high collinearity in the covariate space are contained within known covariate groupings. To assuage variance inflation due to multicollinearity we propose the group inverse-gamma gamma (GIGG) prior, a heavy-tailed prior that can trade-off between local and group shrinkage in a data adaptive fashion. A special case of the GIGG prior is the group horseshoe prior, whose shrinkage profile is correlated within-group such that the regression coefficients marginally have exact horseshoe regularization. We show posterior consistency for regression coefficients in linear regression models and posterior concentration results for mean parameters in sparse normal means models. The full conditional distributions corresponding to GIGG regression can be derived in closed form, leading to straightforward posterior computation. We show that GIGG regression results in low mean-squared error across a wide range of correlation structures and within-group signal densities via simulation. We apply GIGG regression to data from the National Health and Nutrition Examination Survey for associating environmental exposures with liver functionality., 44 pages, 4 figures
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- 2021
17. Assessing the added value of linking electronic health records to improve the prediction of self-reported COVID-19 testing and diagnosis.
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Clark-Boucher, Dylan, Boss, Jonathan, Salvatore, Maxwell, Smith, Jennifer A., Fritsche, Lars G., and Mukherjee, Bhramar
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ELECTRONIC health records , *COVID-19 testing , *COVID-19 pandemic , *ELECTRONIC records , *COVID-19 , *PREDICTION models - Abstract
Since the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, a focus of research has been to identify risk factors associated with COVID-19-related outcomes, such as testing and diagnosis, and use them to build prediction models. Existing studies have used data from digital surveys or electronic health records (EHRs), but very few have linked the two sources to build joint predictive models. In this study, we used survey data on 7,054 patients from the Michigan Genomics Initiative biorepository to evaluate how well self-reported data could be integrated with electronic records for the purpose of modeling COVID-19-related outcomes. We observed that among survey respondents, self-reported COVID-19 diagnosis captured a larger number of cases than the corresponding EHRs, suggesting that self-reported outcomes may be better than EHRs for distinguishing COVID-19 cases from controls. In the modeling context, we compared the utility of survey- and EHR-derived predictor variables in models of survey-reported COVID-19 testing and diagnosis. We found that survey-derived predictors produced uniformly stronger models than EHR-derived predictors—likely due to their specificity, temporal proximity, and breadth—and that combining predictors from both sources offered no consistent improvement compared to using survey-based predictors alone. Our results suggest that, even though general EHRs are useful in predictive models of COVID-19 outcomes, they may not be essential in those models when rich survey data are already available. The two data sources together may offer better prediction for COVID severity, but we did not have enough severe cases in the survey respondents to assess that hypothesis in in our study. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Variable selection with multiply-imputed datasets: choosing between stacked and grouped methods
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Du, Jiacong, Boss, Jonathan, Han, Peisong, Beesley, Lauren J, Goutman, Stephen A, Batterman, Stuart, Feldman, Eva L, and Mukherjee, Bhramar
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Methodology (stat.ME) ,FOS: Computer and information sciences ,Statistics::Methodology ,Applications (stat.AP) ,Statistics - Applications ,Statistics - Computation ,Computation (stat.CO) ,Statistics - Methodology - Abstract
Penalized regression methods, such as lasso and elastic net, are used in many biomedical applications when simultaneous regression coefficient estimation and variable selection is desired. However, missing data complicates the implementation of these methods, particularly when missingness is handled using multiple imputation. Applying a variable selection algorithm on each imputed dataset will likely lead to different sets of selected predictors, making it difficult to ascertain a final active set without resorting to ad hoc combination rules. In this paper we consider a general class of penalized objective functions which, by construction, force selection of the same variables across multiply-imputed datasets. By pooling objective functions across imputations, optimization is then performed jointly over all imputed datasets rather than separately for each dataset. We consider two objective function formulations that exist in the literature, which we will refer to as "stacked" and "grouped" objective functions. Building on existing work, we (a) derive and implement efficient cyclic coordinate descent and majorization-minimization optimization algorithms for both continuous and binary outcome data, (b) incorporate adaptive shrinkage penalties, (c) compare these methods through simulation, and (d) develop an R package miselect for easy implementation. Simulations demonstrate that the "stacked" objective function approaches tend to be more computationally efficient and have better estimation and selection properties. We apply these methods to data from the University of Michigan ALS Patients Repository (UMAPR) which aims to identify the association between persistent organic pollutants and ALS risk., 23 pages, 6 figures. This paper has been submitted to Statistics in Medicine
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- 2020
19. Bridging the gap between Repositories and Homepages - Providing data from DSpace-CRIS with OData
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Boß, Jonathan and Matějka, Cornelius
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REST ,Website integration ,OData ,Repository ,DSpace-CRIS - Abstract
Universities are using a multitude of technical systems to support researchers and students. As a result there are new challenges concerning administration and system integration. The University of Bamberg has the requirement that research data from our repository (DSpace-CRIS) should be accessible through a web service to embed the data into a homepage uitilizing Typo3. DSpace-CRIS already features a REST API which supports access to DSpace's core data (publications) but is not conceived to provide data of CRIS entities (projects, research data). Moreover, in a multitude system landscape it is favored to use the same standard for several systems to access data which is implemented by the Open Data Protocol (OData) at the University of Bamberg. The goal of OData is to establish a consistent standard for realizing a RESTful API. In 2017 OData has been approved as a standard for Open Data Exchange by OASIS. In our approach the OData API makes direct use of DSpace-CRIS' underlying search platform (Solr) to access both DSpace's core data and data of CRIS entities by implementing a unified query language. Providing data from several system with the same query language simplifies the integration within other systems and reduces the amount of maintenance.
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- 2019
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20. A hierarchical integrative group least absolute shrinkage and selection operator for analyzing environmental mixtures.
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Boss, Jonathan, Rix, Alexander, Chen, Yin‐Hsiu, Narisetty, Naveen N., Wu, Zhenke, Ferguson, Kelly K., McElrath, Thomas F., Meeker, John D., and Mukherjee, Bhramar
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JOINTS (Anatomy) ,ENVIRONMENTAL health ,ENVIRONMENTAL sciences ,POISONS ,SAMPLE size (Statistics) - Abstract
Environmental health studies are increasingly measuring multiple pollutants to characterize the joint health effects attributable to exposure mixtures. However, the underlying dose‐response relationship between toxicants and health outcomes of interest may be highly nonlinear, with possible nonlinear interaction effects. Existing penalized regression methods that account for exposure interactions either cannot accommodate nonlinear interactions while maintaining strong heredity or are computationally unstable in applications with limited sample size. In this article, we propose a general shrinkage and selection framework to identify noteworthy nonlinear main and interaction effects among a set of exposures. We design the hierarchical integrative group least absolute shrinkage and selection operator (HiGLASSO) to (a) impose strong heredity constraints on two‐way interaction effects (hierarchical), (b) incorporate adaptive weights without necessitating initial coefficient estimates (integrative), and (c) induce sparsity for variable selection while respecting group structure (group LASSO). We prove sparsistency of the proposed method and apply HiGLASSO to an environmental toxicants dataset from the LIFECODES birth cohort, where the investigators are interested in understanding the joint effects of 21 urinary toxicant biomarkers on urinary 8‐isoprostane, a measure of oxidative stress. An implementation of HiGLASSO is available in the higlasso R package, accessible through the comprehensive R archive network. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Amyotrophic Lateral Sclerosis Survival Associates With Neutrophils in a Sex-specific Manner.
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Murdock, Benjamin J., Goutman, Stephen A., Boss, Jonathan, Kim, Sehee, and Feldman, Eva L.
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- 2021
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22. Untargeted metabolomics yields insight into ALS disease mechanisms.
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Goutman, Stephen A., Boss, Jonathan, Kai Guo, Alakwaa, Fadhl M., Patterson, Adam, Sehee Kim, Savelieff, Masha Georges, Junguk Hur, Feldman, Eva L., Guo, Kai, Kim, Sehee, and Hur, Junguk
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AMYOTROPHIC lateral sclerosis ,METABOLOMICS ,BODY mass index ,ALACHLOR ,LOGISTIC regression analysis ,LIPID metabolism ,BIOCHEMISTRY ,UNSATURATED fatty acids ,RESEARCH ,CARNITINE ,RESEARCH methodology ,ANTI-infective agents ,REGRESSION analysis ,DISCRIMINANT analysis ,CASE-control method ,METABOLISM ,MEDICAL cooperation ,EVALUATION research ,CREATINE ,COMPARATIVE studies ,FATTY acids - Abstract
Objective: To identify dysregulated metabolic pathways in amyotrophic lateral sclerosis (ALS) versus control participants through untargeted metabolomics.Methods: Untargeted metabolomics was performed on plasma from ALS participants (n=125) around 6.8 months after diagnosis and healthy controls (n=71). Individual differential metabolites in ALS cases versus controls were assessed by Wilcoxon rank-sum tests, adjusted logistic regression and partial least squares-discriminant analysis (PLS-DA), while group lasso explored sub-pathway-level differences. Adjustment parameters included sex, age and body mass index (BMI). Metabolomics pathway enrichment analysis was performed on metabolites selected by the above methods. Finally, machine learning classification algorithms applied to group lasso-selected metabolites were evaluated for classifying case status.Results: There were no group differences in sex, age and BMI. Significant metabolites selected were 303 by Wilcoxon, 300 by logistic regression, 295 by PLS-DA and 259 by group lasso, corresponding to 11, 13, 12 and 22 enriched sub-pathways, respectively. 'Benzoate metabolism', 'ceramides', 'creatine metabolism', 'fatty acid metabolism (acyl carnitine, polyunsaturated)' and 'hexosylceramides' sub-pathways were enriched by all methods, and 'sphingomyelins' by all but Wilcoxon, indicating these pathways significantly associate with ALS. Finally, machine learning prediction of ALS cases using group lasso-selected metabolites achieved the best performance by regularised logistic regression with elastic net regularisation, with an area under the curve of 0.98 and specificity of 83%.Conclusion: In our analysis, ALS led to significant metabolic pathway alterations, which had correlations to known ALS pathomechanisms in the basic and clinical literature, and may represent important targets for future ALS therapeutics. [ABSTRACT FROM AUTHOR]- Published
- 2020
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23. Do black/white differences in telomere length depend on socioeconomic status?
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Needham, Belinda L., Salerno, Stephen, Roberts, Emily, Boss, Jonathan, Allgood, Kristi L., and Mukherjee, Bhramar
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TELOMERES ,HEALTH & Nutrition Examination Survey ,SOCIAL marginality - Abstract
Social and economic disadvantage are hypothesized to increase the risk of disease and death via accelerated biological aging. Given that US blacks are socially and economically disadvantaged relative to whites, health disparities scholars expected that blacks would have shorter telomere length–a biomarker of cell aging–than whites. Yet the majority of studies have found that blacks have longer telomere length than whites. Using data from the National Health and Nutrition Examination Survey (n = 3,761; 28.3% non-Hispanic black, 71.7% non-Hispanic white), we found that leukocyte telomere length was 4.00% (95% CI: 1.12%, 6.87%) longer among blacks compared to whites in the full sample, but differences were greatest among those with lower SES (5.66%; 95% CI: 0.10%, 10.32%), intermediate among those with middle SES (4.14%; 95% CI: 0.05%, 8.24%), and smallest among those with higher SES (2.33%; 95% CI: −3.02%, 7.67%). These results challenge purely genetic explanations for race differences in telomere length and point to a potential social-environmental cause of longer telomere length in US blacks. [ABSTRACT FROM AUTHOR]
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- 2020
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24. High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis.
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Goutman, Stephen A., Boss, Jonathan, Patterson, Adam, Mukherjee, Bhramar, Batterman, Stuart, and Feldman, Eva L.
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AMYOTROPHIC lateral sclerosis ,HEALTH risk assessment ,DISEASE risk factors ,BLOOD testing ,SURVIVAL analysis (Biometry) ,PERSISTENT pollutants - Abstract
Objective: To determine whether persistent organic pollutants (POP) affect amyotrophic lateral sclerosis (ALS) survival.Methods: ALS participants seen at the University of Michigan (Ann Arbor, MI, USA) provided plasma samples for measurement of POPs. ALS disease and clinical features were collected prospectively from the medical records. Survival models used a composite summary measure of exposure due to multiple POPs (environmental risk score or ERS).Results: 167 participants (40.7% female, n=68) with ALS were recruited, of which 119 died during the study period. Median diagnostic age was 60.9 years (IQR 52.7-68.2), median time from symptom onset to diagnosis was 1.01 years (IQR 0.67-1.67), bulbar onset 28.7%, cervical onset 33.5% and lumbar onset 37.7%. Participants in the highest quartile of ERS (representing highest composite exposure), adjusting for age at diagnosis, sex and other covariates had a 2.07 times greater hazards rate of mortality (p=0.018, 95% CI 1.13 to 3.80) compared with those in the lowest quartile. Pollutants with the largest contribution to the ERS were polybrominated diphenyl ethers 154 (HR 1.53, 95% CI 0.90 to 2.61), polychlorinated biphenyls (PCB) 118 (HR 1.50, 95% CI 0.95 to 2.39), PCB 138 (HR 1.69, 95% CI 0.99 to 2.90), PCB 151 (HR 1.46, 95% CI 1.01 to 2.10), PCB 175 (HR 1.53, 95% CI 0.98 to 2.40) and p,p'-DDE (HR 1.39, 95% CI 1.07 to 1.81).Conclusions: Higher concentrations of POPs in plasma are associated with reduced ALS survival, independent of age, gender, segment of onset and other covariates. This study helps characterise and quantify the combined effects of POPs on ALS and supports the concept that environmental exposures play a role in disease pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2019
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25. Complete hazard ranking to analyze right-censored data: An ALS survival study.
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Huang, Zhengnan, Zhang, Hongjiu, Boss, Jonathan, Goutman, Stephen A., Mukherjee, Bhramar, Dinov, Ivo D., Guan, Yuanfang, and null, null
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SURVIVAL analysis (Biometry) ,CLINICAL trials ,VECTOR spaces ,GAUSSIAN processes ,AMYOTROPHIC lateral sclerosis - Abstract
Survival analysis represents an important outcome measure in clinical research and clinical trials; further, survival ranking may offer additional advantages in clinical trials. In this study, we developed a non-parametric ranking-based technique to transform patients' survival data into a linear space of hazard ranks. The transformation enables the utilization of machine learning base-learners including Gaussian process regression, Lasso, and random forest on survival data. The method was submitted to the DREAM Amyotrophic Lateral Sclerosis (ALS) Stratification Challenge. Ranked first place, the model gave more accurate ranking predictions on the PRO-ACT ALS dataset in comparison to Cox proportional hazard model. By utilizing right-censored data in its training process, the method demonstrated its state-of-the-art predictive power in ALS survival ranking. Its feature selection identified multiple important factors, some of which conflicts with previous studies. [ABSTRACT FROM AUTHOR]
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- 2017
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26. Association Between Life Purpose and Mortality Among US Adults Older Than 50 Years.
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Alimujiang, Aliya, Wiensch, Ashley, Boss, Jonathan, Fleischer, Nancy L., Mondul, Alison M., McLean, Karen, Mukherjee, Bhramar, and Pearce, Celeste Leigh
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- 2019
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27. Maternal blood metal and metalloid concentrations in association with birth outcomes in Northern Puerto Rico.
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Ashrap, Pahriya, Watkins, Deborah J., Mukherjee, Bhramar, Boss, Jonathan, Richards, Michael J., Rosario, Zaira, Vélez-Vega, Carmen M., Alshawabkeh, Akram, Cordero, José F., and Meeker, John D.
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SEMIMETALS , *PREMATURE labor , *LABOR (Obstetrics) , *PREGNANT women , *HEAVY metals - Abstract
• First study to assess maternal metals in relation to birth outcomes in Puerto Rico. • Highlights the importance of assessing the effects of mixtures on health outcomes. • Pb, even at low-levels, was the most strongly associated with risk of preterm birth. • Elevated Mn and Zn exposure may adversely affect birth outcomes. In previous studies, exposures to heavy metals such as Pb and Cd have been associated with adverse birth outcomes; however, knowledge on effects at low levels of exposure and of other elements remain limited. We examined individual and mixture effects of metals and metalloids on birth outcomes among 812 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort. We measured 16 essential and non-essential metal(loid)s in maternal blood collected at 16–20 and 24–28 weeks gestation. We used linear and logistic regression to independently examine associations between geometric mean (GM) concentrations of each metal across visits and gestational age, birthweight z-scores, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). We evaluated effect modification with infant sex*metal interaction terms. To identify critical windows of susceptibility, birth outcomes were regressed on visit-specific metal concentrations. Furthermore, average metal concentrations were divided into tertiles to examine the potential for non-linear relationships. We used elastic net (ENET) regularization to construct Environmental Risk Score (ERS) as a metal risk score and Bayesian Kernel Machine Regression (BKMR) to identify individual metals most critical to each outcome, accounting for correlated exposures. In adjusted models, an interquartile range (IQR) increase in GM lead (Pb) was associated with 1.63 higher odds of preterm birth (95%CI = 1.17, 2.28) and 2 days shorter gestational age (95% CI = −3.1, −0.5). Manganese (Mn) and zinc (Zn) were also associated with higher odds of preterm birth and shorter gestational age; the associations were strongest among the highest tertile for Mn and among females for Zn. Mercury (Hg) was associated with higher risk of preterm birth at the later window of pregnancy. Ni measured later in pregnancy was associated with lower odds of SGA. ENET and BKMR models selected similar metals as "important" predictors of birth outcomes. The association between ERS and preterm birth was assessed and the third tertile of ERS was significantly associated with an elevated odds ratio of 2.13 (95% CI = 1.12, 5.49) for preterm birth compared to the first tertile. As the PROTECT cohort has lower Pb concentrations (GM = 0.33 μg/dL) compared to the mainland US, our findings suggest that low-level prenatal lead exposure, as well as elevated Mn and Zn exposure, may adversely affect birth outcomes. Improved understanding on environmental factors contributing to preterm birth, together with sustainable technologies to remove contamination, will have a direct impact in Puerto Rico and elsewhere. [ABSTRACT FROM AUTHOR]
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- 2020
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28. Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico.
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Ashrap, Pahriya, Watkins, Deborah J., Mukherjee, Bhramar, Boss, Jonathan, Richards, Michael J., Rosario, Zaira, Vélez-Vega, Carmen M., Alshawabkeh, Akram, Cordero, José F., and Meeker, John D.
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TRACE metals , *PREGNANT women , *TRACE elements , *HEAVY metals , *METALS , *SEMIMETALS , *MICRONUTRIENTS , *URANIUM - Abstract
Given the potential adverse health effects related to toxic trace metal exposure and insufficient or excessive levels of essential trace metals in pregnant women and their fetuses, the present study characterizes biomarkers of metal and metalloid exposure at repeated time points during pregnancy among women in Puerto Rico. We recruited 1040 pregnant women from prenatal clinics and collected urine, blood, and questionnaire data on demographics, product use, food consumption, and water usage at up to three visits. All samples were analyzed for 16 metal(loid)s: arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), titanium (Ti), uranium (U), vanadium (V), and zinc (Zn). Urine samples were additionally analyzed for molybdenum (Mo), platinum (Pt), antimony (Sb), tin (Sn), and tungsten (W). Mean concentrations of most metal(loid)s were higher among participants compared to the general US female population. We found weak to moderate correlations for inter-matrix comparisons, and moderate to strong correlations between several metal(loid)s measured within each biological matrix. Blood concentrations of Cu, Zn, Mn, Hg, and Pb were shown to reflect reliable biomarkers of exposure. For other metals, repeated samples are recommended for exposure assessment in epidemiology studies. Predictors of metal(loid) biomarkers included fish and rice consumption (urinary As), fish and canned food (blood Hg), drinking public water (blood Pb), smoking (blood Cd), and iron/folic acid supplement use (urinary Cs, Mo, and Sb). Characterization of metal(loid) biomarker variation over time and between matrices, and identification of important exposure sources, may inform future epidemiology studies and exposure reduction strategies. • First study to assess exposure to multiple metal(loid)s among pregnant women in Puerto Rico. • Concentration of most metals among pregnant women were higher than women of same age in NHANES. • Reliable biomarkers of exposures identified by examining biomarkers over time and between matrices. • Exposure predictors: fish, rice-As, fish-Hg, public water-Pb, smoking-Cd, supplement-Cs, Mo, and Sb.. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank.
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Jin W, Boss J, Bakulski KM, Goutman SA, Feldman EL, Fritsche LG, and Mukherjee B
- Abstract
Background and Objectives: Amyotrophic lateral sclerosis (ALS) causes profound impairments in neurological function and a cure for this devastating disease remains elusive. Early detection and risk stratification are crucial for timely intervention and improving patient outcomes. This study aimed to identify predisposing genetic, phenotypic, and exposure-related factors for Amyotrophic lateral sclerosis using multi-modal data and assess their joint predictive potential., Methods: Utilizing data from the UK Biobank, we analyzed an unrelated set of 292 ALS cases and 408,831 controls of European descent. Two polygenic risk scores (PRS) are constructed: "GWAS Hits PRS" and "PRS-CS," reflecting oligogenic and polygenic ALS risk profiles, respectively. Time-restricted phenome-wide association studies (PheWAS) were performed to identify pre-existing conditions increasing ALS risk, integrated into phenotypic risk scores (PheRS). A poly-exposure score ("PXS") captures the influence of environmental exposures measured through survey questionnaires. We evaluate the performance of these scores for predicting ALS incidence and stratifying risk, adjusting for baseline demographic covariates., Results: Both PRSs modestly predicted ALS diagnosis, but with increased predictive power when combined (covariate-adjusted receiver operating characteristic [AAUC] = 0.584 [0.525, 0.639]). PheRS incorporated diagnoses 1 year before ALS onset (PheRS1) modestly discriminated cases from controls (AAUC = 0.515 [0.472, 0.564]). The "PXS" did not significantly predict ALS. However, a model incorporating PRSs and PheRS1 improved prediction of ALS (AAUC = 0.604 [0.547, 0.667]), outperforming a model combining all risk scores. This combined risk score identified the top 10% of risk score distribution with a 4-fold higher ALS risk (95% CI: [2.04, 7.73]) versus those in the 40%-60% range., Discussions: By leveraging UK Biobank data, our study uncovers predisposing ALS factors, highlighting the improved effectiveness of multi-factorial prediction models to identify individuals at highest risk for ALS., Competing Interests: Potential Conflicts of Interest LGF is a Without Compensation (WOC) employee at the VA Ann Arbor, a United States government facility.
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- 2024
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30. Statistical methods for chemical mixtures: a roadmap for practitioners.
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Hao W, Cathey AL, Aung MM, Boss J, Meeker JD, and Mukherjee B
- Abstract
Quantitative characterization of the health impacts associated with exposure to chemical mixtures has received considerable attention in current environmental and epidemiological studies. With many existing statistical methods and emerging approaches, it is important for practitioners to understand when each method is best suited for their inferential goals. In this study, we conduct a review and comparison of 11 analytical methods available for use in mixtures research, through extensive simulation studies for continuous and binary outcomes. These methods fall in three different classes: identifying important components of a mixture, identifying interactions and creating a summary score for risk stratification and prediction. We carry out an illustrative data analysis in the PROTECT birth cohort from Puerto Rico. Most importantly we develop an integrated package "CompMix" that provides a platform for mixtures analysis where the practitioner can implement a pipeline for several types of mixtures analysis. Our simulation results suggest that the choice of methods depends on the goal of analysis and there is no clear winner across the board. For selection of important toxicants in the mixture and for identifying interactions, Elastic net by Zou et al. (Enet), Lasso for Hierarchical Interactions by Bien et al (HierNet), Selection of nonlinear interactions by a forward stepwise algorithm by Narisetty et al. (SNIF) have the most stable performance across simulation settings. Additionally, the predictive performance of the Super Learner ensembling method by Van de Laan et al. and HierNet are found to be superior to the rest of the methods. For overall summary or a cumulative measure, we find that using the Super Learner to combine multiple Environmental Risk Scores can lead to improved risk stratification properties. We have developed an R package "CompMix: A comprehensive toolkit for environmental mixtures analysis", allowing users to implement a variety of tasks under different settings and compare the findings. In summary, our study offers guidelines for selecting appropriate statistical methods for addressing specific scientific questions related to mixtures research. We identify critical gaps where new and better methods are needed.
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- 2024
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31. Do black/white differences in telomere length depend on socioeconomic status?
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Needham BL, Salerno S, Roberts E, Boss J, Allgood KL, and Mukherjee B
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- Adult, Black People psychology, Black People statistics & numerical data, Female, Health Status Disparities, Humans, Male, Middle Aged, United States, Weights and Measures instrumentation, White People psychology, White People statistics & numerical data, Black or African American, Black People classification, Social Class, Telomere classification, White People classification
- Abstract
Social and economic disadvantage are hypothesized to increase the risk of disease and death via accelerated biological aging. Given that US blacks are socially and economically disadvantaged relative to whites, health disparities scholars expected that blacks would have shorter telomere length-a biomarker of cell aging-than whites. Yet the majority of studies have found that blacks have longer telomere length than whites. Using data from the National Health and Nutrition Examination Survey (n = 3,761; 28.3% non-Hispanic black, 71.7% non-Hispanic white), we found that leukocyte telomere length was 4.00% (95% CI: 1.12%, 6.87%) longer among blacks compared to whites in the full sample, but differences were greatest among those with lower SES (5.66%; 95% CI: 0.10%, 10.32%), intermediate among those with middle SES (4.14%; 95% CI: 0.05%, 8.24%), and smallest among those with higher SES (2.33%; 95% CI: -3.02%, 7.67%). These results challenge purely genetic explanations for race differences in telomere length and point to a potential social-environmental cause of longer telomere length in US blacks.
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- 2019
- Full Text
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