Emory University School of Medicine
Emory University School of Medicine
Department of Gynecology and Obstetrics

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Department of Gynecology and Obstetrics

Lab of Alicia Smith, PhD

Research in this lab focuses on the role of genetic and epigenetic variation in predicting behavioral and psychiatric traits.

The development of psychiatric disorders is influenced by specific environmental risk factors, but the mechanism through which this occurs is unclear. The relationship may be direct, or it may occur only in those with a particular genetic susceptibility. Research in this lab focuses on the role of genetic and epigenetic variation in predicting behavioral and psychiatric traits. In particular, we are interested in the prenatal environment and early childhood because evidence suggests that adversity during these critical developmental periods increases the risk of developing childhood behavioral problems and adult psychiatric disorders. Through collaborations, we are also developing analytical strategies for genome-wide DNA methylation data and working with translational animal models. To determine how risk factors such as diet, stress or medication exposure interact with sequence variants or with DNA methylation patterns to promote risk we evaluate:

  1. Prenatal
  2. Child and
  3. Adult cohorts

Collaborators at Emory:

We are an integrated lab with a focus on design, implementation and analysis of high quality genotyping, DNA methylation and RNA expression studies. Ongoing collaborations include investigators at and outside of Emory.

Collaborators Outside of Emory:

Current Studies: Pregnancy Outcomes & Child Development

Epigenetics of Preterm Birth

Preterm birth is a risk factor for child behavior problems and adult psychiatric disorders. We have shown that DNA methylation across the genome associates with gestational age in term deliveries and in spontaneous preterm birth. The goal of this project is to identify PTB-associated epigenetic differences in maternal and fetal samples and to evaluate whether those differences provide insight into the pathophysiology of PTB and development of psychopathology.

Epigenetic Biomarkers of Early Psychotropic Medication Exposure

The use of antipsychotics, antidepressants, and antiepileptics in both pre-pubertal and post-pubertal windows of brain development raise concerns about the functional effects of psychotropic exposure. We recently identified DNA methylation differences in umbilical cord blood of children exposed to prenatal antiepileptics but not antipsychotics or antidepressants. This ongoing project will evaluate the relationship between these epigenetic differences and social, affective and cognitive functioning in early childhood.

Epigenetic and Biobehavioral Determinants of Preterm Birth in Black Women

The proposed research will investigate whether biobehavioral factors linked to PTB influence the regulation and expression of genes to promote PTB in AA women. We will focus our investigation on biobehavioral factors that affect the inflammatory pathway – including poor nutritional status, stress, and reproductive tract infections – as, according to the Institute of Medicine, inflammation predominantly contributes to the excessive rates of PTB experienced by AA women. This research will contribute to a biopsychosocial understanding of within-race risk for PTB, providing insight into important risk and protective factors relevant to AA women who disproportionately experience PTB. 

Maternal and Child Microbiome

Changes in the microbiome over pregnancy are not well characterized in African American women, and may contribute to an increased risk of adverse pregnancy outcomes, potentially by inducing changes in gene expression. This study will examine the associations between the oral, vaginal, and gut microbiomes with peripheral DNA methylation and gene expression changes over pregnancy to provide a better understanding of how these factors may work together to increase risk of pregnancy complications.

Current Studies: Adult Psychiatric Problems

Genetic and trauma-related risk factors for PTSD

Exposure to early life stress increases the risk of developing posttraumatic stress disorder (PTSD), but not everyone who experiences abuse or trauma develops it. This study explores the genetic and epigenetic correlates of post-traumatic stress disorder in inner-city residents exposed to traumatic events.

Evaluation of PTSD Biomarker Candidates in Fear-Conditioned Mice

We and others have identified DNA methylation differences in the peripheral blood of subjects with PTSD, but it is not clear how these differences relate to epigenetic patterns in the brain or to gene expression. This project evaluates mRNA expression and DNA methylation in the brain and peripheral tissue of fear-conditioned mice.

Current Studies: Methods Development

Nuclear Capture for Cell-Type Specific Epigenetic Analysis of Adipocytes

The goal of this exploratory research grant is to generate monoclonal antibodies to adipocyte-specific nuclear membrane antigens, which can be used to affinity purifying adipocyte nuclei for further molecular genetic and epigenetic analysis. Development of this technology will contribute to research, diagnostics and therapeutics on the numerous diseases descending from obesity and demonstrate the utility of using nuclear membrane antigens to purify nuclei for studies in many other fields of medicine, where cell type specific analyses are needed.

We are very thankful to the following organizations for supporting this work

Software Distribution

Predict Gestational Age from Cord Blood

Gestational age is a commonly used proxy of developmental maturity, and DNA methylation has been shown to be associated with gestational age. Gestational age at birth can be predicted from 148 CpG sites on the 27K or 450K arrays, within about a week of clinically-estimated gestational age.

MethLAB

MethLAB is a GUI package for the analysis of DNA methylation microarray data.

The latest version of MethLAB and its supporting files can be downloaded here: 

MAC 
Windows
Example Files
Tutorial

This repository is a supplement to MethLAB: A graphical user interface package for the analysis of array-based DNA methylation data