The overall objective of this supplemental project is to use microarray genotyping technology to answer new questions about genetic risk factors for two important women's health problems: posttraumatic stress disorder (PTSD) and preterm birth (PTB). PTSD affects 1 in 10 U.S. women, and PTB affects more than 1 in 10 pregnancies. Both conditions have complex causation, including potential gene x environment interactions, and both have heritability estimates in the 25-35% range. We will test two broad hypotheses. First, that PTSD is associated with genetic variants in three physiological stress-response systems (hypothalamic-pituitary-adrenal (HPA) axis, serotonergic, and adrenergic systems). Second, that PTB is associated with genetic variants in five pathways to preterm birth (inflammatory, stress, decidual hemorrhage, uterine disrension, toxins). Using a custom 1.5K SNP panel microarray, we will genotype 10 PTSD risk candidate and 10 PTB candidate genes on 15-20 SNPs each, and perform haplotype analyses. We will also genotype on ca.100 ancestry informative markers. We will conduct case-control gene association tests with cases of PTSD (Aim 1a) and preterm birth (Aim 2a), and quantitative trait analysis with gestational age at birth (Aim 2b). We then will explore the relative contribution to vulnerability of any genetic associations by integrating significant genetic variants into regression models from the parent study containing diagnostic and psychosocial variables (Aim 3). The parent study tests the hypothesis that PTSD is associated with adverse outcomes of childbearing. It is a prospective, multi-site, observational study enrolling a sample of 1,230 women, 40% of whom are African Americans living in Detroit, the city with one of the highest rates of preterm birth: 14.6% overall and 18.4% among African Americans. The parent study's design is well-suited to genetic studies that look for vulnerability to PTSD and PTB because it includes a PTSD-diagnosed cohort and a trauma-exposed, but PTSD-negative (resilient) cohort, which is the ideal design for PTSD genetics research. Risk factors for PTB are measured prospectively. 40% representation of African American women permits analyses from a health disparities perspective. Identification of genetic risk factors for PTSD and PTB will advance our understanding of these two costly disorders, which could lead to better treatments, and perhaps open the door to preventive interventions. The overall objective of this supplemental project is to combine parent grant psychiatric and perinatal data and micro array technology to answer new questions about genetic risk factors for two important women's health problems: posttraumatic stress disorder (PTSD) and preterm birth. Both PTSD and preterm birth are common, each affecting more than 1 in 10 U.S. women. Preterm birth is also the leading cause of perinatal mortality in the United States and the largest area of perinatal health disparity by race. Identification of genetic risk factors for PTSD and for preterm birth will advance our understanding of these costly disorders, lead us to better treatments, and perhaps open the door to preventive interventions. ? ? ?
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