Social genomics is a rapidly emerging area of research that interrelates social experiences with gene expression and, in turn, morbidity and mortality. This field has focused on mRNA transcription profiles of leukocytes (white blood cells) and their implications for the immune system. Such research (including experimental human studies) has revealed that social experiences (e.g., social status and stressors) have the capacity to up-regulate genes associated with pro-inflammatory immune response and down-regulate genes associated with antiviral immune response. This gene expression profile is highly significant for population health because leading causes of morbidity and mortality-cardiovascular diseases (including hypertension and diabetes), autoimmune disorders, some neoplasties, and depression-are inflammatory in their origins. Thus, social genomics examines a major mechanism by which social experiences get under the skin. However, social genomic studies are limited by small, unrepresentative samples; cross-sectional designs; and a paucity of social measures. The proposed research addresses these limitations by leveraging an existing venous blood draw in Wave V of the National Longitudinal Study of Adolescent to Adult Health (Add Health) to:
Aim 1 : Collect an additional 2.5 ml of blood from ~14,000 Add Health respondents at Wave V for gene expression profiling and biobanking of these specimens for follow-up analyses;
Aim 2 : Extract and quality check mRNA and conduct genome-wide transcriptional profiling on the specimens from a large representative subsample of 5,000 respondents;
Aim 3 : Prepare quality-curated transcriptome data and technical documentation of the 5,000 respondents for dissemination and deposit into the NIH Gene Expression Omnibus online repository (GEO) for public use;
Aim 4 : Conduct analysis of basic attributes of the transcriptome profiling data on the 5,000 subsample of Add Health respondents, including how leukocyte gene expression profiles are distributed in the population according to sex, race/ethnicity, and socioeconomic background. The resulting data-when merged with fives waves of rich, multilevel, longitudinal, national data spanning 20 years beginning in early adolescence and including birth records-will provide an unprecedented opportunity to study how multilevel, longitudinal experiences (including circumstances of birth and exposure to toxicants) are associated with disparities in gene expression (and concurrent biomarkers and morbidities) across the US population. These new data could inform therapeutic interventions; target diverse interventions in the population; and identify new mechanistic modes of social circumstance and health, new G candidates in GxE research, and new molecular precipitants (biomarkers) of disease risk before onset of frank illness. Banked specimens will also allow for cutting-edge extensions that include follow-up studies of gene regulation with epigenomic and proteomic studies.
The proposed data collection and dissemination of genome-wide mRNA expression profiles among Add Health respondents make possible for the first time cutting-edge, population-based gene expression studies that map connections among social experiences, the genetic regulation of the immune system, biomarkers, and very common forms of inflammatory morbidity and morbidity-specific mortality. No other data source has: the depth of longitudinal social, behavioral, environmental, genetic, and biological data; the breadth of multilevel longitudinal environmental exposures including the social, physical, and developmental environments over three decades of the life course; or the race, ethnic, socioeconomic status, and geographic diversity of Add Health's national sample. Analyses of these data could inform therapeutic interventions; identify new genetic mechanisms for GxE research; inform mechanistic models that link social circumstances with health (thus targeting interventions and raising awareness about the consequences of social circumstances); and identify new molecular precipitants to disease, allowing for uniquely targeted interventions before the onset of frank illness.
