Technological advances have made genomic sequencing more affordable, efficient, and available. Questions related to the implementation and effects of large-scale sequencing in healthcare have been approached in a largely theoretical manner. To address this knowledge gap, we describe our experience and preliminary results after implementation of several longitudinal genome-based studies.
We are approximately five years post-initiation of studies; the initial goal for the main study is 5,000 trio-based families. This study focuses on trio-based whole-genome sequencing (WGS) and related ‘omics. We enroll in the 2nd trimester via 5 obstetric clinics. We perform WGS from samples taken concurrently with routine newborn screening (infant) and as part of prenatal care (parents). We follow participants longitudinally to investigate the causes of a variety of conditions and to determine best practices for prospective genomic medicine. All data and analysis are cloud-based, allowing storage and management of petabytes of data while maximizing security. We gather data into a unified system by collecting standard HER information, and combine these data with study-specific data. To address study needs and provide services for our healthcare system, we have built a dedicated clinical genomics unit. In addition to our large study, we have smaller studies that focus on unearthing Mendelian explanations.
Over 3000 participating parent-infant trios have been enrolled to date (~60 new families/month). The participation rate of eligible, approached families is ~35%. Our study-specific survey return rate is ~84% per month. Our cohort is extremely diverse, which has enabled us to construct population-specific algorithms for the filtering of variants. We describe a number of Mendelian and non-Mendelian case studies to illustrate our findings.