Genetic Analyses For Epidemiologic Studies Of Respiratory Disease

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

This project describes the role of the lab of Stephanie London in the Immunity, Inflammation and Disease Laboratory in support of her epidemiologic studies. The laboratory is engaged in genetic and epigenetic analyses to support Dr. London’s epidemiologic projects. The lab supports follow-up of findings from our genome wide association studies of pulmonary function and epigenome-wide analyses of smoking. Human genome wide association studies (GWAS) are well designed to identify novel association with pulmonary and other traits. GWAS studies take advantage of correlation across the genome to find these associations. But this correlation makes it difficult to identify the causal variants or even the causal genes. Experimental models can help establish that a GWAS gene is causal. We had previously published two papers where we confirmed human GWAS findings for HTR4 in a knock out mouse model (PMID: 25342126 and PMID: 28130264). We developed conditional mouse models for LRP1. We found that the smooth muscle knockout of LRP1 differs in baseline pulmonary function compared to wild-type mice (PMID: 332901780). The ADAM19 we had the unexpected finding that the knock was not whole body lethal. There were pulmonary phenotypes. The paper is in press at the journal Lung. We have added a new project to follow-up on human epigenome wide association studies (EWAS) of smoking. We used a new methylation array from Illumina combining epigenome wide murine content as well as cross-mammalian content. We completed the exposure of 32 mice in each group (sham and smoke exposed for 6 weeks) last year. We now have the analyses in lung, blood and bone marrow for methylation, lung and blood for RNAseq, lung and blood for metabolomics and lung for proteomics. Statistical analysis have recently been completed and a manuscript is being crafted. Dr. Stephanie London retired May 31 2025 and is currently working on this project as an Emeritus Investigator/Special Volunteer. After May 31 2025 her staff were reassigned to others and are no longer paid for work on these projects.