Genetic Analyses For Epidemiologic Studies Of Respiratory Disease

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

This project describes the role of the lab of Stephanie London in the Laboratory of Respiratory Biology in support of her epidemiologic studies. The laboratory is engaged in genetic and epigenetic analyses to support Dr. Londons 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 and that the there is a pulmonary phenotype. A manuscript is being prepared for submission to a journal. We have added a new project to follow-up on human epigenome wide association studies (EWAS) of smoking. We will be using a new methylation array combining epigenome wide murine content as well as cross-mammalian content. If signatures are seen for exposure in adult animals we will design studies of prenatal exposure. We will also design studies to examine whether these signals can be attenuated by dietary interventions.