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. Efforts for the Personalized Environment and Genes Study has continued, and expanded. Last 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. THis year we have started publishing exciting findings from the cohort. The exposome, which represents all exposures of an individual's life, has recently become a larger area of study in the context of human health and disease. While the exposome is becoming more studied, many studies have ignored underrepresented populations which often have disparate exposure rates. Further, there is a lack of studies that examine many exposures and their associations with many different diseases. To address the gaps in existing work, we wanted to examine a set of common complex diseases, namely asthma, allergic rhinitis, atherogenic heart disease, high cholesterol, hypertension, fibroids, ovarian cysts, bone loss, lower GI polyps, iron deficient anemia, type 2 diabetes, and migraines. Using the NIEHS backed Personalized Environment and Gene Study (PEGS) cohort, which is an multi ancestry cohort based in North Carolina, we can study the exposome and its impact on human health and disease across populations. PEGS has collected survey exposome data that investigates lifestyle, occupational and hobby exposures. To examine the associations with health and the exposome, we have used the Exposome Wide Association Study (ExWAS) framework which is a single exposure model to examine the associations between the exposures and each disease of interest. The present these results, we will be launching the PEGS Explorer website that will serve as a central location to view the results of the ExWAS, as well as the correlations between all of the PEGS exposures. This website launch will be an important tool in the sharing of exposure science results to the scientific community and will serve as a resource for other groups to replicate and extend our results. The prevalence rate of hypertensive disorders of pregnancy (HDP) has persisted in the United States, where there are stark racial and ethnic disparities among those affected. These disparities can be attributed to the lack of research advancement in this area, and broadly, in the obstetrics field, due to the historical exclusion of pregnant people in biomedical research. In collaboration with the University of Cambridge Department of Obstetrics and Gynecology, this project focuses on the genetic and environmental contributions to HDP. We utilize genome-wide association studies to assess genetic variation related to HDP in the Personalized Environment and Genes Study (PEGS) cohort, the UK Biobank (UKBB) cohort, and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. Other aims include downstream analyses, such as fine-mapping, meta-analyses, and considering functional variation through gene-set analyses and pathway enrichment analyses. Exposome-wide association study in PEGS and UKBB can inform candidate environmental exposures that can be used in assessing gene-environment interaction and performing Mendelian randomization for causal inference. Other ongoing efforts include testing the association of HLA variants and adult onset asthma, in expanding the use of polygenic risk scores across traits, and other efforts. I have also expanded collaborations with Dr. Stephanie London's group in both epigenetic and now microbiome data analysis. Continued collaborations with investigators at the EPA and NCSU are also ongoing.