Collaborative Applied Statistics

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

As an interdisciplinary scientist, I work with a number of collaborators both within and outside the NIEHS and applied studies. Such collaborations provide the opportunity to be involved in high impact science, and to realize important gaps in current methods that inspire methods development work. In a collaborative project with Dr. Urmila Kodavanti at the U.S. EPA, we showed that ozone alters liver gene expression for metabolic processes through neuroendocrine activation. Ozone-induced lung injury, hyperglycemia, glucose intolerance, and increases in circulating cholesterol, triglycerides, and leptin were similar in rats with HV and sham surgery. However, decreases in circulating insulin and increased HDL and LDL were observed only in ozone-exposed HV rats. Ozone exposure resulted in changed liver gene expression in both sham and HV rats , however, HV did not change expression in air-exposed rats. Upstream target analysis revealed that ozone-induced transcriptomic changes were similar to responses induced by glucocorticoid-mediated processes in both sham and HV rats. The directionality of ozone-induced changes reflecting cellular response to stress, metabolic pathways, and immune surveillance was similar in sham and HV rats. Along with Dr. Stephanie London's lab, we conducted a genome-wide association study for lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top genetic variants, after clumping based on distance and linkage disequilibrium. We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions. Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma. Also with Dr. London, we conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma. We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression. No associations were observed with atopy without asthma. Numerous cytosinephosphateguanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9108). In a collaboration originally started at NCSU with Dr. Jessica Weems, we analyzed a study to evaluate which rapid blood administration technique causes the least iatrogenic hemolysis in canine packed red blood cells as determined by plasma free hemoglobin and percent hemolysis. The aliquots of each unit were subjected to the following admin- istration techniques: gravity-driven , an infusion pump at maximal rate, appli- cation of a pressure bag, manual compression, and syringe bolus. Compared to the control, there were no significant increases in % hemolysis or plasma fHb noted among any of the trial methods. Despite a storage time of 14 days, 15% of pRBC units had unsuitable hemolysis before even being subjected to the trials. Commonly used rapid infusion techniques in small animal transfusion medicine do not cause significant iatrogenic hemolysis of canine pRBCs in vitro, although a significant risk is present in stored blood. In collaboration with Dr. Trepanier at the University of Wisconsin, hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants. We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and non- boxers using the comet assay. We also compared GST variants and questionnaire- based environmental exposures in boxers with and without lymphoma. Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. Additionally, efforts for the Personalized Environment and Genes Study has continued, and expanded. This year, we collected whole genome sequencing data on 4700 individuals, that also have survey based and GIS based exposure data. We have conducted analyses and built pipelines for genome-wide association analysis, for exposome wide association analysis, and polygenic risk score analysis. We have worked through quality control for the data, and have completed analyses evaluating the genetic risk factors, environmental exposures, and their interactions for Type 2 Diabetes, cardiovascular diseases and outcomes, asthma, and allergic rhinitis.