LELAND STANFORD JUNIOR UNIVERSITY, THE
Grant: $2,141,528 - National Institutes of Health - Sep. 25, 2009
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Award Description: Recent research on Very Low Birth Weight (VLBW) infants suggests that genetic factors account for 50 – 80% of the variance in their susceptibility to bronchopulmonary dysplasia (BPD). Because California has for the past 3 decades stored Guthrie blood spots from all infants in a manner suitable for genomic analysis, and Stanford hosts the State’s database on neonatal care and outcomes (California Perinatal Quality Care Collaborative (CPQCC)), we can link genetic, biomarker, clinical and outcomes data on virtually all ill newborns in California. This population–based study of California infants will identify heritable factors predisposing to BPD, a severe disorder of the pulmonary and cardiovascular systems that results in life long problems, and provide a 'proof of principle' that existing clinical databases and biologic samples permit research into genetic and environmental factors leading to diseases that have their origins during fetal and perinatal life. It has been determined that in California 3,608 infants required continuous oxygen supplementation at 36 weeks post-conceptual age during the calendar years of 2006 through 2008, inclusive. A single blood spot contains 100ul of whole blood and a portion of the spot is sufficient for suitable amplification of DNA to interrogate the genome. Specific aims are to: identify 1000 cases meeting enrollment criteria for BPD and 1000 controls without supplemental oxygen at 36 weeks post-conceptual age that are matched for gender and race for a case-control interrogation of their genomes; link the genetic, biomarker and clinical care and outcomes of identified case and control infants; extract good quality DNA from the Guthrie blood spots of identified case and control infants, amplify and use in microarray analysis of a matched population-based sample of infants with and without BPD; identify heritable factors and suggest key pathophysiologic pathways responsible for BPD that may lead to clinical trials to prevent the disease or modify long-term outcomes for premature infants. The identification of such mutations and genes would have a widespread impact on health care and health delivery for all age groups because it would allow identification of individuals at risk for BPD and suggest key pathophysiologic pathways responsible for the disorder, enabling clinical trials to prevent or modify the course of the disease. The study would also provide 'proof of principle that California’s incredible and unique clinical databases and population-based biologic samples of over 14 million individuals can be harnessed to obtain clinical insight into a specific disease, and thus would enable other research aimed at discovering genetic and environmental factors leading to any disease that has origins during the fetal or perinatal period, including neurodevelopmental abnormalities, blindness, and osteopenia. Therefore, it has the potential for broad impact on other important childhood or adult disorders and provides valuable resources to all the Institutes of the NIH and the public.
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