Nasa Sinnott-Armstrong, PhD, Frontiers In Human Genetics Conference, October 11, 2024

Complex Dynamics Underpin Gene-Environment Interactions

ABSTRACT

Human disease risk is conferred primarily through a complex set of environmental and behavioral exposures throughout life. These exposures are shaped by individual genetic factors, as well as by large-scale environmental forces like climate change, in a highly structured fashion. One common exposure of interest is to pathogenic agents. Here, we focus on the tick-borne illness Lyme disease. We previously conducted a genome-wide association study (GWAS) for Lyme disease and discovered a single strong association with a common missense variant in the gene SCGB1D2. SCGB1D2 is part of the mammal-specific secretoglobin family of short, secreted proteins with no known function. In vitro experiments suggest that SCGB1D2, and possibly other secretoglobins, form a novel mammalian bacterial defense system. We also discovered novel associations between Lyme disease and diseases of the female reproductive tract, informed by community partners, patients, and evidence of tissue-specific function of SCGB1D2. Together, these findings highlight the relationship between genetic and environmental contributions to disease risk. Overall, combined use of statistical and experimental methods, community-engaged research approaches, and computational modeling can improve our understanding of human disease.