Project Grant K23MD019315

AN INTEGRATED OMICS APPROACH TO NEIGHBORHOOD DISADVANTAGE AND PRETERM BIRTH IN BLACK WOMEN - NON-HISPANIC BLACK WOMEN HAVE A 1.5 TIMES GREATER RISK TO HAVE A PRETERM BIRTH (PTB) THAN NON-HISPANIC WHITE WOMEN. THIS INEQUITY IN PTB IS NOT FULLY EXPLAINED BY LOW SOCIOECONOMIC STATUS OR POOR PHYSICAL HEALTH. BLACK PREGNANT WOMEN MORE OFTEN LIVE IN DISADVANTAGED NEIGHBORHOODS WITH HIGHER DISORDER AND CRIME THAN WHITE WOMEN. WOMEN LIVING IN DISADVANTAGED NEIGHBORHOODS EXPERIENCE HIGHER LEVELS OF PSYCHOLOGICAL STRESS. YET, THE BIOLOGICAL PATHWAYS BY WHICH NEIGHBORHOOD DISADVANTAGE AND PSYCHOLOGICAL STRESS INCREASE PTB REMAIN UNCLEAR. GLUCOCORTICOIDS (GCS) MEDIATE THE STRESS RESPONSE, AND THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS CONTROLS GC SECRETION. CHRONIC STRESS EXPOSURES CAN DYSREGULATE THE HPA AXIS AND ALTER GC LEVELS. PREGNANCY MAINTENANCE AND PARTURITION DEPEND UPON A DELICATE PRO- AND ANTI-INFLAMMATORY BALANCE. GCS EXERT POTENT ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS. IN CONTRAST, MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF), WHICH IS ALSO RELEASED IN RESPONSE TO STRESS, EXHIBITS PRO-INFLAMMATORY EFFECTS THAT OVERRIDE GC'S SUPPRESSION OF INFLAMMATION. NEIGHBORHOOD DISADVANTAGE AND LOW SES ARE ASSOCIATED WITH GREATER INFLAMMATION AND DIFFERENTIAL DNA METHYLATION (DNAM) OF INFLAMMATORY GENES. EPIGENOME-WIDE AND CANDIDATE GENE STUDIES REPORTED RELATIONSHIPS AMONG MATERNAL STRESSORS, DIFFERENTIAL DNAM, AND PTB. THE COMBINED EFFECTS OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) NEAR DNAM SITES MAY MODIFY GENE EXPRESSION, POTENTIALLY INCREASING PTB RISK; BUT THIS POSSIBILITY IS UNEXPLORED. INTEGRATED OMIC APPROACHES MAY CLARIFY MECHANISTIC PATHWAYS TO PTB BY EXPLORING INTEGRATED OMIC DATA SETS. THE GOAL OF THIS STUDY IS TO EXAMINE THE RELATIONSHIPS AMONG PERCEIVED (DISORDER, CRIME) AND OBJECTIVE (CENSUS DATA) NEIGHBORHOOD DISADVANTAGE, PSYCHOLOGICAL STRESS, INTEGRATED SNP AND DNAM DATA, AND PTB IN BLACK WOMEN (90 PTB, 90 TERM BIRTHS). WE WILL LEVERAGE DATA FROM TWO RELATED R01 STUDIES (R01MD018293, MPI GIURGESCU & OHM; R01MD011575; PI GIURGESCU). WE WILL USE SOCIODEMOGRAPHIC, NEIGHBORHOOD, PSYCHOLOGICAL STRESS, DNAM DATA, AND DNA BLOOD SAMPLES FROM THE R01 STUDIES. WE WILL ADD OBJECTIVE CRIME DATA, SCREEN FOR SNP VARIANTS, AND COMBINE SNP AND DNAM DATA IN AN INTEGRATED ANALYSIS. WE AIM TO: AIM 1. IDENTIFY PTB-ASSOCIATED SNPS IN MIF-MEDIATED GC REGULATION PATHWAY GENES BETWEEN WOMEN WITH PTB AND TERM BIRTHS; AIM 2. (A) IDENTIFY DIFFERENTIAL DNAM OF GENES WITHIN THE MIF-MEDIATED GC REGULATION PATHWAY IN WOMEN WITH PTB COMPARED TO WOMEN WITH TERM BIRTHS, AND (B) DETERMINE THE EXTENT TO WHICH DIFFERENTIAL DNAM OF GENES WITHIN THE MIF-MEDIATED GC REGULATION PATHWAY ASSOCIATE WITH NEIGHBORHOOD DISADVANTAGE, PSYCHOLOGICAL STRESS, AND GESTATIONAL AGE AT BIRTH; AND AIM 3. EXPLORE THE EXTENT TO WHICH DNAM (AIM 2A) IN THE PRESENCE OF SNPS ( AIM 1) MEDIATES THE ASSOCIATION OF NEIGHBORHOOD DISADVANTAGE AND PSYCHOLOGICAL STRESS WITH PTB. THIS STUDY IS THE FIRST STEP TOWARD USING INTEGRATED OMICS DATASETS TO IDENTIFY THE BIOLOGIC-ENVIRONMENTAL PHENOTYPES THAT INCREASE RISK FOR PTB. THE AWARD WILL PROVIDE THE TRAINING REQUIRED FOR AN INDEPENDENT CAREER FOCUSED ON BIRTH EQUITY FOR BLACK WOMEN.