Dr. Ed Silverman

Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Dr. Edwin Silverman is a pulmonologist and genetic epidemiologist whose research focuses on the genetics of chronic obstructive pulmonary disease. He is the Principal Investigator of multiple studies of COPD genetics, including the Boston Early-Onset COPD Study, the Alpha 1-Antitrypsin Genetic Modifiers Study, the NETT Genetics Ancillary Study, and the Transcontinental COPD Genetics Study. He is also one of two Principal Investigators of the COPDGene Study. His recent work has focused on identifying functional genetic variants influencing COPD susceptibility; integrating imaging, physiology, clinical characterization, and genetics to identify COPD subtypes; and defining networks of interacting biological factors in COPD pathogenesis. He is a Professor of Medicine at Brigham and Women’s Hospital and Harvard Medical School, and he is the Chief of the Channing Division of Network Medicine at Brigham and Women’s Hospital.

Session: Pre-Conference Workshop

DAY 1: September 11, 2019 | Pre-Conference Workshop | 9:30 AM - 10:30 AM

From Genetics to Network Medicine in Chronic Obstructive Pulmonary Disease

Ed Silverman, MD, PhD, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Genetic association studies have identified many genomic regions influencing complex disease risk, including chronic obstructive pulmonary disease (COPD). Collaborative genome-wide association studies (GWAS) have identified more than 80 genomic regions associated with COPD. However, the functional genetic variants within these COPD GWAS loci remain largely unidentified, thus limiting translation of these GWAS discoveries to new disease insights. Efforts to understand the biological effects of COPD genetic loci include gene-targeted murine models, integration of additional Omics data, and functional variant identification.

Although GWAS have provided important insights into COPD, single genetic variants are unlikely to explain complex diseases, because perturbations of biological networks, not isolated genes, confer disease risk. A variety of network-based approaches has been used to gain insights into COPD. Gene expression levels were studied in lung tissue samples from COPD cases and control subjects. Although the top COPD GWAS loci were not differentially expressed, genes that interacted with HHIP, FAM13A, and IREB2 were often differentially expressed in these lung tissues. Weighted gene coexpression network analysis implicated B cell proliferation and signaling differences between COPD cases and controls. We also used COPD GWAS genes as seed genes for random walk analysis to identify a disease module within the protein-protein interaction network. A COPD disease network module of 163 genes was created that had significant differences in gene expression between COPD cases and controls in multiple disease-relevant samples. Correlation-based networks, gene regulatory networks, and protein-protein interaction networks provide complementary information regarding complex diseases.

SESSION 1: SYSTEMS/NETWORK MEDICINE IN CLINICAL PRACTICE

Day 2: September 12, 2019 | Session 1 CO-CHAIR | 10:10 AM - NOON

Ed Silverman, MD, PhD, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.