Project Summary Since 2000, the Fragile Families and Child Wellbeing Study (FFCWS) has provided the social science community with data on a longitudinal birth cohort of nearly 5000 American children born in large cities. FFCWS contains a large number of racial and ethnic minorities: 47% Black children, 27% Hispanic children (17% children born to immigrant Hispanic parents). Approximately 40% of the families live below the poverty line. These features make the data unique among other large-scale, longitudinal studies, and thus well-suited for studying the health and wellbeing of vulnerable populations. Under the current award (R01HD076592), our team has developed a large portfolio of genetic, epigenetic and telomere length (TL) data for children at ages 9 and 15 years. While originally funded to produce an analysis of 197 SNP variants in 72 genes (in a subset of the subjects), we have been able to leverage price reductions and other funding to provide genotypes on approximately 3000 children. These data will be made available to the research community this year, as will TL data for all children at 9 and 15 years of age. The DNA methylation effort has expanded to 2200 paired samples of children (at 9 and 15 years) from the originally funded 500 samples. We plan to make these data available in 2020, when measurement is complete. Continuing the tradition of service that has marked FFCWS from the beginning, in the first year of this renewal project, we will: Aim 1, develop a portfolio of relatively new measures to include: a) multiple polygenetic scores (PGS), including several that exploit gene expression or experimental data to enhance the predictive power for particular phenotypes, b) CNV annotated to gene, c) epigenetic constructs for children, such as methylation age, methylation quantitative trait loci (meQTL) and epigenome-wide association study (EWAS)-derived summary scores, based on genetic and DNA methylation data. All of these derived measures would be completed and made publicly available by year 1 of an award. These statistics will provide important new tools for the genetic assessment of ethnic minority populations. Aim 2, genotype the FFCWS mothers with a multi-ethnic array, allowing a study of parental effects on child health, behavior, and wellbeing through both genetic (including genetic nurturance) and social pathways. This work takes on greater value due to recent calls to expand genome- wide work for non-European ancestry (in particular African and Hispanic) individuals and in children. In Aim 3, we explore best practices around collection, processing and storage of DNA for large scale TL research involving saliva, fresh blood, and stored neonatal dried blood spots (nDBS). These experiments will help fuel a consensus conference associated with the Biomarker Network meeting held with the Population Association of America.

Narrative Since 2000, the Fragile Families and Child Wellbeing Study (FFCWS) has provided data on a longitudinal birth cohort of nearly 5000 American children (47% Black, 27% Hispanic). To better understand the relationship between social and physical environment, genetics, and child outcome, we will measure mother genotype and create summary scores and other analyses of mothers’ genotype and previously measured children’s genotype, DNA methylation, and telomere length, relating this data to measures of child health and wellbeing. Since there is concern that measurement of telomere length (an important measure of stress and wellbeing) is often inaccurate, we will provide experimental data on best practices for telomere length measurement.