This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting genetic epidemiology research under the supervision of an advisory committee comprised of highly qualified sponsors and co-investigators. This K23 award in combination with the PI's background in pediatrics, critical care, outcomes research, clinical epidemiology and medical informatics, provides excellent potential for development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complex inflammatory lung diseases. The overall scientific goal of this proposal is to determine the genetic association between severe bronchiolitis in previously healthy infants caused by respiratory syncytial virus (RSV) and the later development of childhood asthma. Using a prospective cohort design, we propose to follow the large population of patients who were hospitalized for confirmed RSV bronchiolitis during infancy at Children's Hospital, Boston from 1990 to 2000 when they reach 3 to 13 years of age to identify those with persistent or new onset wheezing. Using an interviewer-administered questionnaire, we will assess asthma and atopy diagnoses and symptoms and environmental exposures in both biological parents and the index child. Parents will be surveyed every three months over a 2 to 5 year period to assess the persistence of wheezing in their child. Questionnaire findings will be incorporated into a multiple logistic regression model to predict the development of childhood asthma after RSV bronchiolitis in infancy. Blood will be drawn from both parents and the index child for DNA analysis to test for transmission disequilibrium in the distribution of alleles of nitric oxide synthase genes. We hypothesize that genetic mechanisms confer susceptibility to persistent wheezing after RSV bronchiolitis in infancy and that this susceptibility is found in genes regulating nitric oxide synthase. This proposal is vital to the care of the greater than 6 million childhood asthmatics in the United States. Identifying the genes associated with the onset of childhood asthma could lead to targeted interventions aimed at prevention and treatment of this disorder that is increasing at a rate of 5 percent per year.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-F (F1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Below, Jennifer E; Parra, Esteban J; Gamazon, Eric R et al. (2016) Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs. Sci Rep 6:19429
Gottlieb, D J; Hek, K; Chen, T-H et al. (2015) Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study. Mol Psychiatry 20:1232-9
Nettleton, Jennifer A; Follis, Jack L; Ngwa, Julius S et al. (2015) Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry. Hum Mol Genet 24:4728-38
Lemaitre, Rozenn N; Johnson, Catherine O; Hesselson, Stephanie et al. (2014) Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. Heart Rhythm 11:471-7
Randolph, A G; Yip, W-K; Falkenstein-Hagander, K et al. (2014) Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis. Clin Exp Allergy 44:231-7
Qi, Qibin; Kilpeläinen, Tuomas O; Downer, Mary K et al. (2014) FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals. Hum Mol Genet 23:6961-72
Randolph, Adrienne G; Lange, Christoph; Silverman, Edwin K et al. (2005) Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthma-related phenotypes. Am J Respir Crit Care Med 172:687-92
Vitali, Sally H; Randolph, Adrienne G (2005) Assessing the quality of case-control association studies on the genetic basis of sepsis. Pediatr Crit Care Med 6:S74-7
Randolph, Adrienne G; Lange, Christoph; Silverman, Edwin K et al. (2004) The IL12B gene is associated with asthma. Am J Hum Genet 75:709-15
Randolph, Adrienne G; Gonzales, Calle A; Cortellini, Lynelle et al. (2004) Growth of pediatric intensive care units in the United States from 1995 to 2001. J Pediatr 144:792-8

Showing the most recent 10 out of 14 publications