Channing Laboratory - Edwin K. Silverman, MD, PhD

Edwin K. Silverman, MD, PhD

Assistant Professor of Medicine
Harvard Medical School

Associate Physician
Brigham and Women's Hospital

ed.silverman@channing.harvard.edu

Research Interests

I have had an ongoing interest in the genetic epidemiology of complex diseases. My current research involves the genetic epidemiology of obstructive lung diseases including chronic obstructive pulmonary disease (COPD) and asthma. During my graduate work at Washington University, I studied the variable development of pulmonary function impairment in alpha 1-antitrypsin deficiency using epidemiologic techniques, path analysis, segregation analysis, and genotype-by-environment interaction analysis. During my pulmonary medicine clinical training, I was impressed by several young individuals with severe COPD at an early age who should have had alpha 1-antitrypsin deficiency -- but they did not. To determine if additional genetic factors, other than alpha 1-antitrypsin deficiency, can be identified which predispose to COPD, I have been assembling a group of early-onset COPD families. Compared to control subjects, we have found an increased risk for reduced FEV1 and chronic bronchitis among first-degree relatives of early-onset COPD probands. Interestingly, this increased risl to relatives (approximately 3-fold for FEV1 <60%, FEV1 <80% and chronic bronchitis) is exclusively found when current or ex-smoking first-degree relatives are compared to current or ex-smoking control subjects; no increased risk is found among relatives of COPD probands who are lifelong nonsmokers. We are currently performing genotyping with microsatellite markers adjacent to potential candidate loci and linkage analysis with these markers in our early-onset COPD pedigrees. In addition to studying the genetics of early-onset COPD, I am involved in several genetic studies of asthma, including the study of potential genetic influences on the variable response to medications for asthma.

Selected Publications

Silverman EK, Pierce JA, Province MA, Rao DC, Campbell EJ. Variability of pulmonary function in alpha 1-antitrypsin deficiency: Clinical correlates. Ann Int Med 1989;111:982-991. [abstract]

Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'Donnell WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE. Genetic epidemiology of severe early-onset COPD: risk to relatives for airflow obstruction and chronic bronchitis. Am J Resp Crit Care Med 1998;157:1770-8.[abstract]

Burchard EG, Silverman EK, Rosenwasser LJ, Borish L, Yandava C, Pillari A, Weiss ST, Hasday J, Lilly CM, Ford J, Drazen JM. Association between a sequence variant in the IL-4 gene promoter and FEV1 in asthma. Am J Resp Crit Care Med 1999;160:919-922. [abstract]

Celedon JC, Speizer FE, Drazen JM, Weiss ST, Campbell EJ, Carey VJ, Reilly JJ, Ginns L, Silverman EK. Bronchodilator responsiveness and serum total IgE levels in families of probands with severe, early-onset COPD. Eur Resp J 1999; 14:1009-1014. [abstract]

Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniak RM, Chinchilli VM, Cooper DM, Fahy JV, Fish JE, Ford JG, Kraft M, Kunselman S, Lazarus SC, Lemanske RF Jr, Martin RJ, McLean DE, Peters SP, Silverman EK, Sorkness CA, Szefler SJ, Weiss ST, Yandava CN. The effect of the Beta 2-Adrenergic receptor on the response to regular use of albuterol in asthma. Am J Resp Crit Care Med 2000; 162:75-80. [abstract]

Silverman EK, Weiss ST, Drazen JM, Chapman HA, Carey V, Campbell EJ, Denish P, Silverman RA, Celedon JC, Reilly JR, Ginns L, Speizer FE. Gender-related differences in severe, early-onset chronic obstructive pulmonary disease. Am J Resp Crit Care Med 2000; 162: 2152-2158. [abstract]

Grasemann H, Yandava CN, Storm van=s Gravesande K, Deykin A, Pillari A, Ma J, Sonna LA, Lilly C, Stampfer MJ, Israel E, Silverman EK, Drazen JM. A neuronal NO synthase (NOS1) gene polymorphism is associated with asthma. Biochem Biophys Res Commun 2000; 272: 391-394. [abstract]

Celedon JC, Silverman EK, Weiss ST, Wang B, Fang Z, Xu X. Application of an algorithm for the diagnosis of asthma in Chinese families: Limitations and alternatives for the phenotypic assessment of asthma in family-based genetic studies. Am J Resp Crit Care Med 2000; 162:1679-1684. [abstract]

Wechsler ME, Grasemann H, Deykin A, Silverman EK, Yandava CN, Israel E, Wand M, Drazen JM. Exhaled nitric oxide in patients with asthma: Association with NOS1 genotype. Am J Resp Crit Care Med 2000; 162:2043-2047. [abstract]

Silverman EK, Mosley J, Rao DC, Palmer LJ, Province M, Elston RC, Weiss ST, Campbell, EJ. Linkage analysis of alpha 1-antitrypsin deficiency: Lessons for complex diseases. Hum Hered 2001; 52: 223-32. [abstract]

Silverman EK, Mosley JD, Palmer LJ, Barth M, Senter JM, Brown A, Drazen JM, Kwiatkowski DJ, Chapman HA, Campbell EJ, Province MA, Rao DC, Reilly JJ, Ginns LC, Speizer FE, Weiss ST. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: Airflow obstruction and chronic bronchitis phenotypes. Hum Molec Genet 2002; 11:623-632. [abstract]

Silverman EK, Palmer LJ, Mosley JD, Barth M, Senter JM, Brown A, Drazen JM, Kwiatkowski DJ, Chapman HA, Campbell EJ, Province MA, Rao DC, Reilly JJ, Ginns LC, Speizer FE, Weiss ST. Genome-wide Linkage Analysis of Quantitative Spirometric Phenotypes in Severe, Early-Onset Chronic Obstructive Pulmonary Disease. Am J Hum Genet 2002; 70:1229-1239. [abstract]

Demeo DL, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird N, Weiss ST for the CAMP Research Group. Univariate and multivariate family-based association analysis of the IL-13 Arg130Gln polymorphism in the Childhood Asthma Management Program. Genetic Epidemiology 2002; 23: 335-348. [abstract]

Palmer LJ, Celedon JC, Chapman HA, Speizer FE, Weiss ST, Silverman EK. Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease. Hum Molec Genet 2003;12:1199-1210. [abstract]