Using Integrative Omics as Biomarkers and Diagnostic Tools for SIDS

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Project Summary Sudden Infant Death Syndrome (SIDS) is the second leading cause of death (closely behind congenital and genetic abnormalities), in the postneonatal period (infants 1 month to 1 year of age), despite declines in incidence of over 50% following the Back to Sleep (now called the Safe to Sleep) risk reduction campaign. In 2017, 1400 infants in the US died of SIDS. Extensive research has identified a number of epidemiological risk factors for SIDS, and more recent research has begun to provide evidence of a potential role for genetic susceptibility in the pathophysiology of the disorder. In the United States, African American and American Indian/Alaska Native babies, in particular are at higher risk for SIDS. Advances in technology now allow for more exhaustive interrogations of genomic contributors to disease. The goal of this proposal is to comprehensively evaluate genetic and epigenetic determinates of SIDS and identify gene expression, DNA methylation and metabolomics profiles that might serve as novel biomarkers in infants at greater risk of death from SIDS. We will utilize liver, heart and blood specimens from the Chicago Infant Mortality Study (CIMS), the largest known collection of cardiac tissue from SUID deaths in the US and heart and blood specimens from the NIH NeuroBioBank (NBB) to investigate genetic, epigenetic, and transcriptomic influences of SIDS. We will employ an omics approach encompassing next generation sequencing (exome plus RNA), genome wide epigenetics, and metabolomics profiling to identify novel biomarkers that are predictive of SIDS. These findings could lead to diagnostic tests and early detection of high risk infants, resulting in preventative measures to eliminate SIDS. This study will also be the first to successfully use an integrative –Omics approach to address genetic, epigenetic, and metabolomics contributors for SIDS.