Abstract

Uncovering & confirming gene-environment interactions in stress-related psychopathology. The proposed research will to bring together 3 longitudinal cohort studies (comprising 4 cohort samples) in order to create a powerful epidemiological resource for testing hypotheses about gene- environment interaction (GxE), and for replicating these findings. Using this multi-study resource, we seek to identify genetic pathways of stress resistance by studying sets of candidate genes that are hypothesized to moderate the effects of psychosocial stressors (maltreatment, violence victimization, stressful life events) on conduct disorder and depression/anxiety disorders. Methods: The 3 longitudinal cohort studies (comprising 4 cohort samples, with 5000 individuals) are: the Dunedin Multidisciplinary Health and Development Study, the Christchurch Health and Development Study, and the Environmental Risk Study of Behavioral Development. This epidemiological resource will have 4 necessary elements: (a) Four population-representative samples; (b) comparable information about environmental exposures at multiple points in development (e.g., childhood maltreatment; violence victimization; stressful life events); ( c) measures of psychiatric outcomes; and (d) DNA. This resource will be used to carry out hypothesis-driven studies of GxE across different samples and to establish the reproducibility of the results by carrying out cross-study replication tests. Contributions & Significance: The proposed research can make an important translational contribution by identifying replicable GxE interactions in stress-related psychopathology and by laying a foundation for theory development about psychobiological mechanisms in stress resistance versus vulnerability. ? ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH077874-02
Application #
7478023
Study Section
Special Emphasis Panel (ZRG1-HOP-T (02))
Program Officer
Yao, Yin Y
Project Start
2007-08-01
Project End
2011-03-31
Budget Start
2008-04-28
Budget End
2009-03-31
Support Year
2
Fiscal Year
2008
Total Cost
$429,367
Indirect Cost

  Institution

Name
Duke University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Morris, Richard W; Taylor, Amy E; Fluharty, Meg E et al. (2015) Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium. BMJ Open 5:e008808
Adkins, Daniel E; Clark, Shaunna L; Copeland, William E et al. (2015) Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood. Twin Res Hum Genet 18:335-47
Hancox, Robert J; Shin, Hayden H; Gray, Andrew R et al. (2015) Effects of quitting cannabis on respiratory symptoms. Eur Respir J 46:80-7
Taylor, Amy E; Fluharty, Meg E; Bjørngaard, Johan H et al. (2014) Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. BMJ Open 4:e006141
Belsky, Daniel W; Moffitt, Terrie E; Sugden, Karen et al. (2013) Development and evaluation of a genetic risk score for obesity. Biodemography Soc Biol 59:85-100
Belsky, Daniel W; Moffitt, Terrie E; Baker, Timothy B et al. (2013) Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: evidence from a 4-decade longitudinal study. JAMA Psychiatry 70:534-42
Bagshaw, Andrew T M; Horwood, L John; Liu, Youfang et al. (2013) No effect of genome-wide copy number variation on measures of intelligence in a New Zealand birth cohort. PLoS One 8:e55208
Shalev, I; Moffitt, T E; Sugden, K et al. (2013) Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study. Mol Psychiatry 18:576-81
Meier, Madeline H; Caspi, Avshalom; Houts, Renate et al. (2013) Prospective developmental subtypes of alcohol dependence from age 18 to 32 years: implications for nosology, etiology, and intervention. Dev Psychopathol 25:785-800
Gunduz-Cinar, O; MacPherson, K P; Cinar, R et al. (2013) Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Mol Psychiatry 18:813-23

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