The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
BACKGROUND: Vitamin D is associated with lung health in epidemiologic studies, but mechanisms mediating observed associations are poorly understood. This study explores mechanisms for an effect of vitamin D in lung through an in vivo gene expression study, an expression quantitative trait loci (eQTL) analysis in lung tissue, and a population-based cohort study of sequence variants. METHODS: Microarray analysis investigated the association of gene expression in small airway epithelial cells with serum 25(OH)D in adult non-smokers. Sequence variants in candidate genes identified by the microarray were investigated in a lung tissue eQTL database, and also in relation to cross-sectional pulmonary function in the Health, Aging, and Body Composition (Health ABC) study, stratified by race, with replication in the Framingham Heart Study (FHS). RESULTS: 13 candidate genes had significant differences in expression by serum 25(OH)D (nominal p < 0.05), and a genome-wide significant eQTL association was detected for SGPP2. In Health ABC, SGPP2 SNPs were associated with FEV1 in both European- and African-Americans, and the gene-level association was replicated in European-American FHS participants. SNPs in 5 additional candidate genes (DAPK1, FSTL1, KAL1, KCNS3, and RSAD2) were associated with FEV1 in Health ABC participants. CONCLUSIONS: SGPP2, a sphingosine-1-phosphate phosphatase, is a novel vitamin D-responsive gene associated with lung function. The identified associations will need to be followed up in further studies.