Research

Areas of Specialization

Epigenetics of early life adversity, developmental origins of health and disease, biomarkers of stress and disadvantage, racial disparities in complex disease, social determinants of health, human evolutionary and population genetics

CURRENT RESEARCH

DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE:

Biological Embedding of Stress in Children of Mexican Immigrants.

My newest project is an investigation of the stress experiences of children of Mexican-born immigrants living in Nashville. The goal of this project is to determine how stress among immigrant children may become biologically embedded to predispose them to higher rates of cardiometabolic disease later in life. This project is a 3 year study funded by the Foundation for Child Development, which began in the summer of 2014. This study is motivated by the increasing influx of Hispanic immigrants to the US, and the increasing degree of discrimination and stress they are facing in today’s political and economic climate. The specific aims of the study are twofold: 1) To test and refine hypotheses about biological pathways of embedding of stress in Hispanic immigrant children by specifically investigating dysregulation of the hypothalamic pituitary adrenal axis and of the cardiometabolic system in relation to early life stressors; and 2) To examine whether some classes of stressors are more potent than others in dysregulating these processes.

Collaborators: Nanibaa’ Garrison

See our website at: http://www.chicosnashville.org/

Epigenetics in the Bucharest Early Intervention Project
I am currently involved in an interdisciplinary project with collaborators at Tulane, University of Maryland, and Harvard, to understand how early life exposure to stress may alter the epigenome in ways that may ultimately lead to poor health consequences in adulthood. Epigenetics is the study of processes, such as DNA methylation, that modify patterns of gene expression without altering the underlying DNA sequence. Epigenetic mechanisms are especially relevant for understanding early origins of adult health and disease, because they link environmental exposures with potentially long-term changes in gene expression. With a seed grant from the Robert Wood Johnson Foundation, I am exploring levels of methylation in a number of stress-response genes in cheek cells from children raised in orphanages relative to those raised in foster care settings in Bucharest, Romania. In this on-going longitudinal study, children under 30 months of age were randomized into foster care placement and are being compared with those who continued care in institutions. The psychosocial deprivation and neglect of institutional rearing has shown to have long lasting effects on social development, mental health, and cognitive and neural development. This study provides a unique opportunity to explore the association between this extreme form of early childhood deprivation and DNA methylation changes over time.

Collaborators: Stacy Drury, Charles Zeanah, Charles Nelson, Nathan Fox

Relevant Publications:

Non, AL, Hollister, BM, Humphreys KL, Childebayeva A, Esteves, K, Zeanah, C, Fox, NA, Nelson, CA, Drury, SS. DNA methylation at stress-related genes associated with exposure to early life institutionalization. American Journal of Physical Anthropology. (in press)

DNA Methylation, Stress, and Depression During Pregnancy
I am also working with colleagues at the Harvard School of Public Health and the Brigham and Women’s Hospital on a project to understand epigenetic consequences of early life exposure to stress and depression, in utero. With two seed grants from the Robert Wood Johnson Foundation, I have explored levels of methylation for three stress-response genes and a genome-wide repetitive element in and around the placenta. I have also worked on a project to detect genome wide changes in methylation status associated with exposure to maternal depression and antidepressant medications during pregnancy.

Relevant Publications

Non, A.L., Binder, A.M., Barault, L., Rancourt, R.C., Kubzansky, L.D., & Michels, K.B. (2011). DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta. Placenta, 33, 183-187.

Non AL, Binder AM, Kubzansky LD, Michels KB. (2014). Whole-genome methylation analysis of fetal exposure to maternal depression/anxiety and antidepressant use during pregnancy.  Epigenetics 9(7):964-972.

Rewak M., Buka S., Prescott J., De Vivo I., Loucks E., Kawachi I., Non A., Kubzansky L. Race-Related Health Disparities and Biological Aging: Does Rate of Telomere Shortening Differ Across Blacks and Whites? Biological Psychology. 2014 Mar 29; 99C:92-99[Epub ahead of print].

Stress and Cardiometabolic Biomarkers
I have also been exploring a range of cardiometabolic biomarkers that may be affected by psychosocial stress in childhood and in adulthood. This research is motivated by the observation that psychosocial stress is often associated with poor health outcomes, even after accounting for variation in health behaviors, indicating a role for other direct biological mechanisms. To investigate these mechanisms, I utilized cross-sectional data from the Health Professional Follow-Up Study (HPFS) to explore how measures of social support and stress at work and at home associate with a range of biomarkers across a number of physiological systems, including cardiovascular, inflammatory, endothelial function, and immune response. The HPFS is an ongoing cohort study of men’s health established in 1986 by the Harvard School of Public Health. One interesting finding suggests that stress at work is more important than stress at home for predicting elevated measures of endothelial dysfunction in men. I am also currently investigating the effect of early life social disadvantage on cardiometabolic markers and chronic disease in adulthood using data from the ongoing longitudinal National Collaborative Perinatal Project.

Collaborators: Laura Kubzansky, Ichiro Kawachi, Stephen Gilman, David Williams, Stephen Buka, Eric Loucks, Eric Rimm, Allison Appleton, Natalie Slopen

Relevant Publications

Slopen, N., Loucks E.B., Appleton A., Kawachi I., Kubzansky L.D., Non, A.L., Buka S., Gilman S.E. Prenatal versus childhood adversity and elevated inflammation in adulthood: a test of sensitive periods. (in press at Psychoneuroendocrinology).

Slopen N, Non A, Williams DR, Roberts AL, Albert MA. 2014. Childhood adversity, adult neighborhood context, and cumulative biological risk for chronic diseases in adulthood. Psychosomatic medicine 76(7):481-489.

Non AL, Rewak M, Kawachi I., Gilman S., Loucks E, Appleton A., Roman J.C., Buka S, Kubzansky L. (2014). Childhood social disadvantage, cardiometabolic risk, and chronic disease in adulthood. Am J of Epidemiology. (in press)

Non AL, Rimm EB, Kawachi I, Rewak MA, Kubzansky LD (2014). The Effects of Stress at Work and at Home on Inflammation and Endothelial Dysfunction. PLoS ONE 9(4): e94474. doi:10.1371/journal.pone.0094474

RACIAL DISPARITIES IN HEALTH: THE ROLE OF GENETICS AND CULTURE

Integrating methods from social and biological sciences, colleagues at the University of Florida and I have been working to understand the role of genetic ancestry and cultural classification of race in the development of blood pressure in Southeastern Puerto Rico. We have analyzed genetic data(candidate genes and ancestry informative markers and sociocultural data (measures of race, discrimination, SES, etc) in order to simultaneously test for the contribution of genetic and environmental factors to risk of hypertension. We have also examined the role of genetic ancestry relative to education, in predicting blood pressure variation among African Americans and Whites in the Familial Blood Pressure Program Study. This work was supported by an NSF grant BCS-0820687, entitled “Genetic ancestry, race and health disparities: A biocultural approach,” Connie Mulligan (PI).

Collaborators: Connie Mulligan, Lance Gravlee

Relevant Publications

Non, A.L., Gravlee, C.C., & Mulligan, C.J. (2012). Education, genetic ancestry, and blood pressure in African Americans and Whites. American Journal of Public Health (in press).

Non, A.L., Gravlee, C.C., & Mulligan, C.J. (2010). Questioning the importance of genetic ancestry as a contributor to preterm delivery and related traits in African American women. Am J Obstet Gynecol, 202, e12; author reply e12-13.

Gravlee, C.C., Non, A.L., & Mulligan, C.J. (2009). Genetic ancestry, social classification, and racial inequalities in blood pressure in Southeastern Puerto Rico. PLoS One, 4, e6821.

PAST RESEARCH

Human Evolutionary History

I have worked with colleagues at the University of Florida to understand the evolutionary history of populations around the Red Sea Region, which is an important region for the emergence of anatomically modern humans out of Africa, and also for more recent evolutionary history. Using genetic data from the mitochondrial genome, as well as nuclear autosomal variants and sex chromosomes, we have analyzed the evolution and relationships among Jewish populations in Ethiopia and Yemen. We have also analzed non-Jewishpopulations in these two regions to determine the origin and direction of migrations across the Red Sea along the Southern Dispersal Route out of Africa. This work was supported by NSF grant BCS-0518530, entitled “Human dispersals out of Africa: Mitochondrial and Y chromosomal genetic analysis of Eritrean and Omani populations” (PI: Connie Mulligan).

Relevant Publications

Non, A.L., Al-Meeri, A., Raaum, R.L., Sanchez, L.F., & Mulligan, C.J. (2011). Mitochondrial DNA reveals distinct evolutionary histories for Jewish populations in Yemen and Ethiopia. Am J Phys Anthropol, 144, 1-10.

Černý, V, Mulligan CJ, Fernandes V, Silva NM, Alshamali F, Non A, Harich N, Cherni L, El Gaaied AB, Al-Meeri A, and Pereira L (2011) Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia. Mol Biol Evol 28:71-8.

Al-Meeri, A., Non, A.L., Lajoie, T.W., & Mulligan, C.J. (2011). Effect of different sampling strategies for a single geographic region in Yemen on standard genetic analyses of mitochondrial DNA sequence data. Mitochondrial DNA, 22, 66-70.

Cerny, V., Mulligan, C.J., Fernandes, V., Silva, N.M., Alshamali, F., Non, A., et al. (2011). Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia. Mol Biol Evol, 28, 71-78.

Non, A.L., Kitchen, A., & Mulligan, C.J. (2007). Identification of the most informative regions of the mitochondrial genome for phylogenetic and coalescent analyses. Mol Phylogenet Evol, 44, 1164-1171.