Genetics of Stress: Gene–Stress Correlation and Interaction



In this chapter, we review two recent developments in behavioral genetics that bear on the determinants and sequelae of psychological stress. The first addresses genetic influences on exposure to environmental stressors (gene–stress correlation), and the second, the moderation of genetic effects on behavioral and biological phenotypes by stress-related environmental variation (gene–stress interaction). There is now abundant evidence of genetic influence on stressful life events, traumatic experiences, and parenting and early family environments, as well as on stress-protective factors such as social support and networks of social engagement. With respect to gene–stress interactions, preliminary evidence suggests that polymorphic variation in genes of plausible mechanism modulates physiological reactions to acute psychological stressors and variably affects more distal outcomes (e.g., hypertension, posttraumatic stress disorder, aggressive conduct) as a function of exposure to early or recent life stressors. However, failures to confirm at least one prominently reported finding in this literature raise concern regarding the replicability of published gene–stress interactions. In concluding, we consider the implications of pervasive gene–stress correlation for the interpretation of gene–stress interaction and discuss conceptual and methodological issues relating to the selection of candidate genes and environmental moderators.



Preparation of this manuscript was supported, in part, by National Institutes of Health Grants PO1 HL040962 and RO1 HL065137 (SBM), and UO1 DK056993, RO1 AG018384, and RO1 HL072819 (JMM).


  1. Agrawal, A., Jacobson, K. C., Prescott, C. A., and Kendler, K. S. (2002). A twin study of sex differences in social support. Psychol Med, 32, 1155–1164.PubMedCrossRefGoogle Scholar
  2. Amstadter, A. B., Koenen, K. C., Ruggiero, K. J., Acierno, R., Galea, S. et al (2009). Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. J Anxiety Disord, 23, 369–373.PubMedCrossRefGoogle Scholar
  3. Bartels, M., de Geus, E. J. C., Kirschbaum, C., Sluyter, F., and Boomsma, D. (2003). Heritability of daytime cortisol levels in children. Behav Genet, 33, 421–433.PubMedCrossRefGoogle Scholar
  4. Beevers, C. G., Gibb, B. E., McGeary, J. E., and Miller, I. A. (2007). Serotonin transporter genetic variation and biased attention for emotional word stimuli among psychiatric inpatients. J Abnorm Psychol, 116, 208–212.PubMedCrossRefGoogle Scholar
  5. Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B. et al (2009). Vulnerability genes or plasticity genes? Mol Psychiatry, 14, 746–754.PubMedCrossRefGoogle Scholar
  6. Bennett, A. J., Lesch, K. P., Heils, A., Long, J. C., Lorenz, J. G. et al (2002). Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry, 7, 118–122.PubMedCrossRefGoogle Scholar
  7. Bhagwagar, Z., Whale, R., and Cowen, P. J. (2002). State and trait abnormalities in serotonin function in major depression. Br J Psychiatry, 180, 24–28.PubMedCrossRefGoogle Scholar
  8. Billig, J. P. Hershberger, S. L., Iacono, W. G., and McGue, M. (1996). Life events and personality in late adolescence: genetic and environmental relations. Beh Genet, 26, 542–554.Google Scholar
  9. Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C. et al (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299, 1291–1305.PubMedCrossRefGoogle Scholar
  10. Binder, E. B., Salyankina, D., Lichner, P., Wochnik, G. M., Ising, M., et al (2004). Polymorphisms in FDBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet, 36, 1319–1325.PubMedCrossRefGoogle Scholar
  11. Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P. et al (2008). Influence of child abuse on adult depression: moderation by the corticotrophin-releasing hormone gene. Arch Gen Psychiatry, 65, 190–200.PubMedCrossRefGoogle Scholar
  12. Brown, G. W., and Harris, T. (1978). Social Origins of Depression. New York: Free Press.Google Scholar
  13. Brown, G. W., and Harris, T. O. (2008). Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene–environment interaction. J Affect Disord, 111, 1–12.PubMedCrossRefGoogle Scholar
  14. Brown, G. W., Harris, T. O., and Hepworth, C. (1995). Loss, humiliation and entrapment among women developing depression: a patient and non-patient comparison. Psychol Med, 25, 7–22.PubMedCrossRefGoogle Scholar
  15. Brown, S. M., Peet, E., Manuck, S. B., Williamson, D. E., Dahl, R. E. et al (2005). A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol Psychiatry, 10, 884–888.PubMedCrossRefGoogle Scholar
  16. Canli, T., Congdon, E., Gutknecht, L., Constable, R. T., and Lesch, K. P. (2005). Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation. J Neural Transm, 112, 1479–1485.PubMedCrossRefGoogle Scholar
  17. Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J. et al (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851–854.PubMedCrossRefGoogle Scholar
  18. Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W. et al (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTTLPR gene. Science, 301, 386–389.PubMedCrossRefGoogle Scholar
  19. Cohen, S., Janicki-Deverts, D., and Miller, G. E. (2007). Psychological stress and disease. JAMA, 298, 1685–1687.PubMedCrossRefGoogle Scholar
  20. Cohen, S., Kamarck, T., and Mermelstein, R. (1983). A global measure of perceived stress. J Health Soc Behav, 24, 385–396.PubMedCrossRefGoogle Scholar
  21. Cohen, S., Kessler, R. C., and Gordon, L. U. (1995). Strategies for measuring stress in studies of psychiatric and physical disorders. In S. Cohen, R.C. Kessler, & L. U. Gordon (Eds.), Measuring Stress (pp. 3–28). New York: Oxford University Press.Google Scholar
  22. Cohen, S., Tyrrell, D. A. J., and Smith, A. P. (1993). Negative life events, perceived stress, negative affect, and susceptibility to the common cold. J Pers Soc Psychol, 64, 131–140.PubMedCrossRefGoogle Scholar
  23. Cohen, S., and Wills, T. A. (1985). Stress, social support and the buffering hypothesis. Psychol Bull, 98, 310–357.PubMedCrossRefGoogle Scholar
  24. DeRijk, R. H., Wust, S., Meijer, O. C., Zennaro, M.-C., Federenko, I. S. et al (2006). A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. J Clin Endocrinol Metab, 91, 5083–5089.PubMedCrossRefGoogle Scholar
  25. Ducci, F., Enoch, M.-A., Hodgkinson, C., Zu, K., Catena, M., Robin, R. W. et al (2008). Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women. Mol Psychiatry, 13, 334–347.PubMedCrossRefGoogle Scholar
  26. Ellis, B. J. (2004). Timing of pubertal maturation I girls: an integrated life history approach. Psychol Bull, 130, 920–958.PubMedCrossRefGoogle Scholar
  27. Enoch, M.-A., Steer, C. D., Newman, T. K., Gibson, N., and Goldman, D. (2010). Early life stress, MAOA, and gene–environment interactions predict behavioral disinhibition in children. Genes Brain Behav, 13, 1122–1130.Google Scholar
  28. Fakra, E., Hyde, L. W., Gorka, A., Fischer, P. M., Munoz, K. E. et al (2009). Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Arch Gen Psychiatry, 66, 33–40.PubMedCrossRefGoogle Scholar
  29. Federenko, I. S., Nagamine, M., Hellhammer, D. H., Wadhwa, P. D., and Wust, S. (2004). The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent. J Clin Endocrinol Metab, 89, 6244–6250.PubMedCrossRefGoogle Scholar
  30. Federenko, I. S., Schlotz, W., Kirschbaum, C., Bartels, M., Hellhammer, D. H. et al (2006). The heritability of perceived stress. Psychol Med, 36, 375–385.PubMedCrossRefGoogle Scholar
  31. Flory, J. D., Mann, J. J., Manuck, S. B., and Muldoon, M. F. (1998). Recovery from major depression is not associated with normalization of serotonergic function. Biol Psychiatry, 43, 320–326.PubMedCrossRefGoogle Scholar
  32. Foley, D. L., Eaves, L. J., Wormley, B., Silberg, J. L., Maes, H. H. et al (2004). Childhood adversity, monamine oxidase A genotype, and risk for conduct disorder. Arch Gen Psychiatry, 61, 738–744.PubMedCrossRefGoogle Scholar
  33. Foley, D. L., Neale, M. C., and Kendler, K. S. (1996). A longitudinal study of stressful life events assessed at interview with an epidemiological sample of adult twins: the basis of individual variation in event exposure. Psychol Med, 26, 1239–1252.PubMedCrossRefGoogle Scholar
  34. Fowler, J. H., Dawes, C. T., and Christakis, N. A. (2009). Model of genetic variation in human social networks. Proc Natl Acad Sci USA, 106, 1720–1724.PubMedCrossRefGoogle Scholar
  35. Ge, D., Zhu, H., Huang, Y., Treiber, F. A., Harshfield, G. A. et al (2007). Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects. Hypertension, 49, 107–112.PubMedCrossRefGoogle Scholar
  36. Ge, X., Conger, R. D., Cadoret, R. J., Neiderhiser, J. M., Yates, W. et al (1996). The developmental interface between nature and nurture: a mutual influence model of child antisocial behavior and parent behaviors. Dev Psychol, 32, 574–589.CrossRefGoogle Scholar
  37. Gianaros, P. J., Bleil, M. E., Muldoon, M. F., Jennings, J. R., Sutton-Tyrrell, K. et al (2002). Is cardiovascular reactivity associated with atherosclerosis among hypertensives. Hypertension, 40, 742–747.PubMedCrossRefGoogle Scholar
  38. Gitlin, M. J. (2009). Pharmacotherapy and other somatic treatments for depression. In I. H. Gotlib & C. L. Hammen (Eds.), Handbook of Depression, 2nd Ed (pp. 554–585). New York: Guildford.Google Scholar
  39. Gotlib, I. H., Joormann, J., Minor, K. L., and Hallmayer, J. (2008). HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry, 63, 847–851.PubMedCrossRefGoogle Scholar
  40. Grove, M. L., Morrison, A., Folsom, A. R., Boerwinkle, E., Hoelscher, D. M. et al (2007). Gene–environment interaction and the GNB3 gene in the Atherosclerosis Risk in Communities Studies. Int J Obes, 31, 919–926.CrossRefGoogle Scholar
  41. Hariri, A. R., Gorka, A., Hyde, L. W., Kimak, M., Halder, I. et al (2009). Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiatry, 66, 9–16.PubMedCrossRefGoogle Scholar
  42. Headey, B., and Wearing, A. (1989). Personality, life events, and subjective well-being: toward a dynamic equilibrium model. J Pers Soc Psychol, 57, 731–739.CrossRefGoogle Scholar
  43. Hershberger, S. L., Lichtenstein, P., and Knox, S. S. (1994). Genetic and environmental influences on perceptions of organizational climate. J Appl Psychol, 79, 24–33.PubMedCrossRefGoogle Scholar
  44. Humphries, S. E., Hawe, E., Dhamrait, S., Miller, G. J., and Talmud, P.J. (2003). In search of genetic precision. Lancet, 361, 1908–1909.PubMedCrossRefGoogle Scholar
  45. Humphries, S. E., Talmud, P. J., Hawe, E., Bolla, M., Day, I. N. M. et al (2001). Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study. Lancet, 358, 115–119.PubMedCrossRefGoogle Scholar
  46. Ising, M., Depping, A.-M., Sliebertz, A., Lucae, S., Unschuld, P. G. et al (2008). Polymorphisms in the FDBP5 gene region modulate recovery from psychosocial stress in health controls. Eur J Neurosci, 28, 389–398.PubMedCrossRefGoogle Scholar
  47. Jabbi, M., Korf, J., Kema, I. P., Hartman, C., and van der Pompe, G. et al (2007). Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA. Mol Psychiatry, 12, 483–490.PubMedGoogle Scholar
  48. Jacobson, K. C., and Rowe, D. C. (1999). Genetic and environmental influences on the relationships between family connectedness, school connectedness, and adolescent depressed mood: sex differences. Dev Psychol, 35, 926–939.PubMedCrossRefGoogle Scholar
  49. Jang, K. L., Stein, M. B., Taylor, S., Asmundson, G. J., and Livesley, W. J. (2003). Exposure to traumatic events and experiences: aetiological relationships with personality function. Psychiatry Res, 120, 61–69.PubMedCrossRefGoogle Scholar
  50. Jang, K. L., Vernon, P. A., Livesley, W. J., Stein, M. B., and Wolf, H. (2001). Intra- and extra-familial influences on alcohol and drug misuse: a twin study of gene–environment correlation. Addiction, 96, 1307–1318.PubMedCrossRefGoogle Scholar
  51. Jennings, J. R., Kamarck, T. W., Everson-Rose, S. A., Kaplan, G. A., Manuck, S. B. et al (2004). Exaggerated blood pressure responses during mental stress are prospectively related to enhanced carotid atherosclerosis in middle-aged Finnish men. Circulation, 110, 2198–2203.PubMedCrossRefGoogle Scholar
  52. Johnson, W., McGue, M., Krueger, R. F., and Bouchard, T. J. (2004). Marriage and personality: a genetic analysis. J Pers Soc Psychol, 86, 285–294.PubMedCrossRefGoogle Scholar
  53. Kendler, K. S. (1997). Social support: a genetic-epidemiologic analysis. Am J Psychiatry, 154, 1398–1404.PubMedGoogle Scholar
  54. Kendler, K. S., and Baker, J. H. (2007). Genetic influences on measures of the environment: a systematic review. Psychol Med, 37, 615–626.PubMedCrossRefGoogle Scholar
  55. Kendler, K. S., Gardner, C. O., and Prescott, C. A. (2003a). Personality and the experience of environmental adversity. Psychol Med, 22, 1193–1202.CrossRefGoogle Scholar
  56. Kendler, K. S., Hettema, J. M., Butera, F., Gardner, C. O., and Prescott, C. A. (2003b). Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Arch Gen Psychiatry, 60, 789–796.PubMedCrossRefGoogle Scholar
  57. Kendler, K. S., Karkowski, L. M., and Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry, 156, 837–841.PubMedGoogle Scholar
  58. Kendler, K. S., Kessler, R. C., Walters, E. E., MacLean, C., Neale, M. C. et al (1995). Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatry, 152, 833–842.PubMedGoogle Scholar
  59. Kendler, K. S., Thornton, L. M., and Gardner, C. O. (2000). Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the ‘kindling” hypothesis. Am J Psychiatry, 63, 1113–1120.Google Scholar
  60. Keskitalo, K., Tuorila, H., Spector, T. D., Cherkas, L. F., Knaapila, A. et al (2008). The three-factor eating questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations. Am J Clin Nutr, 88, 263–271.PubMedGoogle Scholar
  61. Kessler, R. C., Kendler, K. S., Heath, A., Neale, M. C., and Eaves, L. J. (1992). Social support, depressed mood, and adjustment to stress: a genetic epidemiologic investigation. J Pers Soc Psychol, 62, 257–272.PubMedCrossRefGoogle Scholar
  62. Kilpatrick, D. G., Koenen, K. C., Ruggiero, K. J., Acierno, R., Galea, S. et al (2007). The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry, 164, 1693–1699.PubMedCrossRefGoogle Scholar
  63. Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R. et al (2006). MAOA, maltreatment, and gene–environment interaction predicting children’s mental health: new evidence and a meta-analysis. Mol Psychiatry, 11, 903–913.PubMedCrossRefGoogle Scholar
  64. Kivimaki, M., Virtanen, M., Elovainio, M., Kouvonen, A., Vaanaanen, A. et al (2006). Work stress in the etiology of coronary heart disease – a meta-analysis. Scand J Work Environ Health, 32, 431–442.PubMedCrossRefGoogle Scholar
  65. Koenen, K. C., Aiello, A. E., Bakshis, E., Amstadter, A. B., Ruggiero, K. J. et al (2009). Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. Am J Epidemiol, 169, 704–711.PubMedCrossRefGoogle Scholar
  66. Koenen, K. C., Harley, R., Lyons, M. J., Wolfe, J., Simpson, J. C. et al (2002). A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder. J Nerv Ment Dis, 190, 209–218.PubMedCrossRefGoogle Scholar
  67. Koenen, K. C., Szxe, G., Purcell, S., Smoller, J. W., Bartholomew, D. et al (2005). Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry, 10, 1058–1059.PubMedCrossRefGoogle Scholar
  68. Krantz, D. S., and Manuck, S. B. (1984). Acute psychophysiologic reactivity and risk of cardiovascular disease: a review and methodologic critique. Psychol Bull, 96, 435–463.PubMedCrossRefGoogle Scholar
  69. Krueger, R. F., Markon, K. E., and Bouchard, T. J. (2003). The extended genotype: the heritability of personality accounts for the heritability of recalled family environments in twins reared apart. J Pers, 71, 809–833.PubMedCrossRefGoogle Scholar
  70. Kumsta, R., Entringer, S., Koper, J. W., van Rossum, E. F. C., Hellhammer, D. H. et al (2007). Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biol Psychiatry, 62, 683–689.CrossRefGoogle Scholar
  71. Kupper, N., de Geus, E. J. C., van den Berg, M., Kirschbaum, C., Boomsma, E. I. et al (2005). Familial influences on basal salivary cortisol in an adult population. Psychoneuroendocrinology, 30, 857–868.PubMedCrossRefGoogle Scholar
  72. Landsbergis, P. A., Schnall, P. L., Pickering, T. G., Warren, K., and Schwartz, J. E. (2003). Life-course exposure to job strain and ambulatory blood pressure in men. Am J Epidemiol, 157, 998–1006.PubMedCrossRefGoogle Scholar
  73. Lazarus, R. W., and Folkman, S. (1984). Stress, Appraisal and Coping. New York: Springer.Google Scholar
  74. Li, G. H., Faulhaber, H. D., Rosenthal, M., Schuster, H., Jordan, J. et al (2001). Beta-2 adrenergic receptor gene variations and blood pressure under stress in normal twins. Psychophysiology, 38, 485–489.PubMedCrossRefGoogle Scholar
  75. Lu, Y., Zhu, H., Wang, X., Snieder, H., Huang, Y. et al (2006). Effects of dopamine receptor type 1 and Gs Protein α subunit gene polymorphisms on blood pressure at rest and in response to stress. Am J Hypertens, 19, 832–836.PubMedCrossRefGoogle Scholar
  76. Lyons, M. J., Goldberg, J., Eisen, S. A., True, W., Tsuang, M. T. et al (1993). Do genes influence exposure to trauma? A twin study of combat. Am J Med Genet, 48, 22–27.PubMedCrossRefGoogle Scholar
  77. Magnus, K., Diener, E., Fujita, F., and Pavot, W. (1993). Extraversion and neuroticism as predictors of objective life events: a longitudinal analysis. J Pers Soc Psychol, 65, 1046–1053.PubMedCrossRefGoogle Scholar
  78. Mann, J. J., Huang, Y.-Y., Underwood, M. D., Kassir, S. A., Oppenheim, S. et al (2000). A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding I major depression and suicide. Arch Gen Psychiatry, 57, 729–738.PubMedCrossRefGoogle Scholar
  79. Manuck, S. B. (1994). Cardiovascular reactivity in cardiovascular disease. Int J Behav Med, 1, 4–31.PubMedCrossRefGoogle Scholar
  80. Manuck, S. B. (in press). The reaction norm in gene x environment interaction. Mol Psychiatry.Google Scholar
  81. Manuck, S. B., Flory, J. D., Ferrell, R. E., and Muldoon, M. F. (2004). Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region. Psychoneuroendocrinology, 29, 651–668.PubMedCrossRefGoogle Scholar
  82. Manuck, S. B., Harvey, A. H., Lechleiter, S. L., and Neal, S. K. (1978). Effects of coping on blood pressure responses to threat of aversive stimulation. Psychophysiology, 15, 544–549.PubMedCrossRefGoogle Scholar
  83. Manuck, S. B., Marsland, A. L., Flory, J. D., Gorka, A., Ferrell, R. E. et al (2010). Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men. Psychoneuroendocrinology, 35, 94–104.Google Scholar
  84. Marsland, A. L., Bachen, E. A., Cohen, S., Rabin, B., Manuck, S. B. (2002). Stress, immune reactivity and susceptibility to infectious disease. Physiol Behav, 77, 711–716.PubMedCrossRefGoogle Scholar
  85. McCaffery, J. M., Bleil, M., Pogue-Geile, M. F., Ferrell, R. E., and Manuck, S. B. (2003). The association between a serotonin transporter gene variant and cardiovascular reactivity in young adult male and female twins. Psychosom Med, 65, 721–728.PubMedCrossRefGoogle Scholar
  86. McCaffery, J. M., Papandonatos, G. D., Bond, D. S., Lyons, M. J., and Wing, R. R. (2009). Gene X environment interaction of vigorous exercise and body mass index among male Vietnam-era twins. Am J Clin Nutr, 89, 1011–1018.PubMedCrossRefGoogle Scholar
  87. McCaffery, J. M., Papandonatos, G. D., Lyons, M. J., and Niaura, R. (2008). Educational attainment and the heritability of self-reported hypertension among male Vietnam-era twins. Psychosom Med, 70, 781–786.PubMedCrossRefGoogle Scholar
  88. McCaffery, J. M., Pogue-Geile, M. F., Ferrell, R. E., Petro, N., and Manuck, S. B (2002). Variability within alpha- and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge. J Hypertens, 20, 1105–1114.PubMedCrossRefGoogle Scholar
  89. McCaffery, J. M., Pogue-Geile, M. F., Muldoon, M. F., Debski, T. T., Wing, R. R. et al (2001). The nature of the association between diet and serum lipids in the community: a twin study. Health Psychol, 20, 341–350.PubMedCrossRefGoogle Scholar
  90. McDermott, R., Tingley, D., Cowden, J., Frazzetto, G., and Johnson, D. D. P. (2009). Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. Proc Natl Acad Sci USA, 106, 2118–2123.PubMedCrossRefGoogle Scholar
  91. McGue, M., and Lykken, D. (1992). Genetic influence on risk of divorce. Psycho Sci, 3, 368–373.CrossRefGoogle Scholar
  92. Meikle, A. W., Stringham, J. D., Woodward, M. G., and Bishop, D. T. (1988). Heritability of variation in plasma cortisol levels. Metabolism, 37, 514–517.PubMedCrossRefGoogle Scholar
  93. Meyer-Lindenberg, A., Buckholtz, S. W., Kolachana, B. R., Hariri, A. R., Pezawas, L. et al (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA, 103, 6269–6274.PubMedCrossRefGoogle Scholar
  94. Middeldorp, C. M., Cath, D. C., Vink, J. M., and Boomsma, D. I. (2005). Twin and genetic effects on life events. Twin Res Hum Genet, 8, 224–231.PubMedCrossRefGoogle Scholar
  95. Moffitt, T. E., Caspi, A., and Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry, 62, 473–481.PubMedCrossRefGoogle Scholar
  96. Moffitt, T. E., Caspi, A., and Rutter, M. (2006). Measured gene–environment interactions in psychopathology. Perspectives on Psychological Science, 1, 5–27.CrossRefGoogle Scholar
  97. Monroe, S. M., and Kelley, J. M. (1995). Measurement of stress appraisal. In S. Cohen, R. C. Kessler, & L. U. Gordon (Eds.), Measuring Stress (pp. 122–147). New York: Oxford University Press.Google Scholar
  98. Monroe, S. M., and Reid, M. W. (2008). Gene–environment interactions in depression research: genetic polymorphisms and life-stress polyprocedures. Psychol Sci, 19, 947–956.PubMedCrossRefGoogle Scholar
  99. Monroe, S. M., Slavich, G. M., and Georgiades, K. (2009). The social environment and life stress in depression. In I. H. Gotlib & C. L. Hammen (Eds.), Handbook of Depression, 2nd Ed (pp. 340–360). New York: Guildford.Google Scholar
  100. Munafo, M. R., Brown, S. M., and Hariri, A. R. (2008). Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry, 63, 852–857.PubMedCrossRefGoogle Scholar
  101. Munafo, M. R., Durrant, C., Lewis, G., and Flint, J. (2009). Gene X environment interactions at the serotonin transporter locus. Biol Psychiatry, 65, 211–219.PubMedCrossRefGoogle Scholar
  102. Munafo, M. R., and Flint, J. (2004). Meta-analysis of genetic association studies. Trends Genet, 20, 439–444.PubMedCrossRefGoogle Scholar
  103. Nelson, T. L., Fingerlin, T. E., Moss, L. K., Barmada, M. M., Ferrell, R. E. et al (2007). Association of the peroxisome proliferator-activated receptor γ gene with type 2 diabetes mellitus varies by physical activity among non-Hispanic whites from Colorado. Metabolism, 56, 388–393.PubMedCrossRefGoogle Scholar
  104. O’Connor, T. G., Deater-Deckard, K., Fulker, D., Rutter, M., and Plomin, R. (1998). Genotype–environment correlations in late childhood and early adolescence: antisocial behavioral problems and coercive parenting. Dev Psychol, 34, 970–981.PubMedCrossRefGoogle Scholar
  105. Ohlin, B., Berglund, G., Nilsson, P., and Melander, O. (2007). Job strain, decision latitude and alpha2B-adrenergic receptor polymorphisms significantly interact and associate with higher blood pressures in men. J Hypertens, 25, 1613–1619.PubMedCrossRefGoogle Scholar
  106. Ohlin, B., Berglund, G., Nilson, P. M., and Melander, O. (2008). Job strain, job demands and adrenergic beta1-receptor-polymorphism: a possible interaction affecting blood pressure in men, J Hypertens, 26, 1583–1589.PubMedCrossRefGoogle Scholar
  107. Ohlin, B., Berglund, G., Rosvall, M., and Nilsson, P. M. (2007). Job strain in men, but not in women, predicts a significant rise in blood pressure after 6.5 years follow-up. J Hypertens, 25, 525–531.PubMedCrossRefGoogle Scholar
  108. Ordovas, J. M., Corella, D., Demissie, S., Cuupples, A., Couture, P. et al (2002). Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism. Circulation, 106, 2315–2321.PubMedCrossRefGoogle Scholar
  109. Osinsky, R., Reuter, M., Kupper, Y., Schmitz, A., Kozyra, E. et al (2008). Variation in the serotonin transporter gene modulates selective attention to threat. Emotion, 8, 584–588.PubMedCrossRefGoogle Scholar
  110. Parsey, R. V., Hastings, R. S., Oquendo, M. A., Hu, X., Goldman, D. et al (2006). Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain. Am J Psychiatry, 163, 48–51.PubMedCrossRefGoogle Scholar
  111. Perez-Edgar, K., Bar-Haim, Y., McDermott, J., Gerodetsky, E., Hodgkiinson, C. A. et al (2010). Variations in the serotonin-transporter gene are associated with attention bias patterns to positive and negative emotion faces. Biol Psychol, 83, 269–271.Google Scholar
  112. Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A. et al (2009). Protective effects of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch Gen Psychiatry, 66, 978–985.PubMedCrossRefGoogle Scholar
  113. Poulton, R. G., and Andrews, G. (1992). Personality as a cause of adverse life events. Acta Psychiatr Scand, 85, 35–38.PubMedCrossRefGoogle Scholar
  114. Plomin, R. (1994). Genetics and Experience. Thousand Oaks, CA: Sage.Google Scholar
  115. Plomin, R., DeFries, J. C., McClearn, G. E., and McGuffin, P. (2008). Behavioral Genetics, 5th Ed. New York: Worth.Google Scholar
  116. Plomin, R., Lichtenstein, P., Pedersen, N. L., McClearn, G. E. and Nesselroade, J. R. (1990). Genetic influence on life events during the last half of the life span. Psychol Aging, 5, 25–30.PubMedCrossRefGoogle Scholar
  117. Plomin, R., McClearn, G. E., Pedersen, N., Nesselroade, J. R., and Bergeman, C. S. (1988). Genetic influence on childhood family environment perceived retrospectively from the last half of the life span. Dev Psychol, 24, 738–745.CrossRefGoogle Scholar
  118. Plomin, R., McClearn, G. E., Pedersen, N., Nesselroade, J. R., and Bergeman , C. S. (1989). Genetic influence on adult’s ratings of their current family environment. J Marriage Fam, 51, 791–803.CrossRefGoogle Scholar
  119. Prom-Wormley, E. C., Eaves, L. J., Foley, D. L., Gardner, C. O., Archer, K. J. et al (2009). Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females. Psychol Med, 39, 579–590.PubMedCrossRefGoogle Scholar
  120. Pruessner, M., Hellhammer, D. H., Pruessner, J. C., and Lupien, S. J. (2003). Self-reported depressive symptoms and stress levels in health young men: associations with the cortisol response to awakening. Psychosom Med, 65, 92–99.PubMedCrossRefGoogle Scholar
  121. Rankinen, T., Rice, T., Leon, A. S., Skinner, J. S., Wilmore, J. H. et al (2002). G protein β3 polymorphism and hemodynamic and body composition phenotypes in the HERITAGE family study. Physiol Genom 8, 151–157.Google Scholar
  122. Rao, F., Zhang, L., Wessel, J., Zhang, K., Wen, G. et al (2008). Adrenergic polymorphism and the human stress response. Ann NY Acad Sci, 1148, 282–296.PubMedCrossRefGoogle Scholar
  123. Raynor, D. A., Pogue-Geile, M. F., Kamarck, T. W., McCaffery, J. M., and Manuck, S. B. (2002). Covariation of psychosocial characteristics associated with cardiovascular disease: genetic and environmental influences. Psychosom Med, 64, 191–203.PubMedGoogle Scholar
  124. Reist, C., Mazzanti, C., Vu, R., Tran, D., and Goldman, D. (2001). Serotonin transporter promoter polymorphism is associated with attenuated prolactive response to fenfluramine. Am J Med Genet, 105, 363–368.PubMedCrossRefGoogle Scholar
  125. Risch, N., Herrell, R., Lehner, T., Liang, K. Y., Eaves, L. et al (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA, 301, 2462–2471.PubMedCrossRefGoogle Scholar
  126. Saudino, K. J., Pedersen, N. L., Lichtenstein, P., McClearn, G. E., and Plomin, R. (1997). Can personality explain genetic influences on life events? J Pers Soc Psychol, 72, 196–206.PubMedCrossRefGoogle Scholar
  127. Schlotz, W., Hellhammer, D. H., Schulz, P., and Stone, A. A. (2004). Perceived work overload and chronic worrying predict weekend-weekday differences in cortisol awakening response. Psychosom Med, 66, 207–214.PubMedCrossRefGoogle Scholar
  128. Schnoll, R. A., Johnson, T. A., and Lerman, C. (2007). Genetics of smoking behavior. Curr Psychiatry Rep, 9, 349–357.PubMedCrossRefGoogle Scholar
  129. Shioe, K., Ichimiya, T., Suhara, T., Takano, A., Sudo, Y. et al (2003). No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse, 48, 184–188.PubMedCrossRefGoogle Scholar
  130. Sibille, E., and Lewis, D. A. (2006). SERT-ainly involved in depression, but when? Am J Psychiatry, 163, 1–3.CrossRefGoogle Scholar
  131. Siegrist, J., Starke, D., Chandola, T., godin, I., Marmot, M. et al (2004). The measurement of effort-reward imbalance at work: European comparisons. Soc Sci Med, 58, 1483–1499.PubMedCrossRefGoogle Scholar
  132. Snieder, H., Harshfield, G. A., Barbeau, P., Pollock, D. M., Pollock, J. S., et al (2002). Dissecting the genetic architecture of the cardiovascular and renal stress response. Biol Psychol, 61, 73–95.PubMedCrossRefGoogle Scholar
  133. Spotts, E. L., Neiderhiser, J. M., Towers, S. H., Hansson, K., Lichtenstein, P. et al (2004). Genetic and environmental influences on marital relationships. J Fam Psychol, 18, 107–118.PubMedCrossRefGoogle Scholar
  134. Stein, M. B., Jang, K. L., Taylor, S., Vernon, P. A., and Livesley, W. J. (2002). Genetic and environmental influences. Am J Psychiatry, 159, 1675–1681.PubMedCrossRefGoogle Scholar
  135. Steptoe, A., van Jaarsveld, C. H. M., Semmler, C., Plomin, R., and Wardle, J. (2009). Heritability of daytime cortisol levels and cortisol reactivity in children. Psychoneuroendocrinology, 34, 273–280.PubMedCrossRefGoogle Scholar
  136. Stubbe, J. H., Boomsma, D. I., Vink, J. M., Cornes, B. K., Martin, H. G. et al (2006). Genetic influences on exercise participation in 37,051 twin pairs from seven countries. PLos One 1, e22.PubMedCrossRefGoogle Scholar
  137. Tai, E. S., Corella, D., Deurenberg-Yap, Cutter, J., Chew, S. K. et al (2003). Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: The 1998 Singapore National Health Survey. J Nutr, 133, 3399–3409.PubMedGoogle Scholar
  138. Talmud, P. J. (2004). How to identify gene–environment interactions in a multifactorial disease: CHD as an example. Proc Nutr Soc, 63, 5–10.PubMedCrossRefGoogle Scholar
  139. Talmud, P. J., Bujac, S. R., Hall, S., Miller, G. J., and Humphries, S. E. (2000). Substitution of asparagines for aspartic acid at residue 9 (D9N) of lipoprotein lipase markedly augments risk of ischaemic heart disease in male smokers. Atherosclerosis, 149, 75–81.PubMedCrossRefGoogle Scholar
  140. Taylor, A., and Kim-Cohen, J. (2007). Meta-analysis of gene–environment interactions in developmental psychopathology. Dev Psychopathol, 19, 1029–1037.PubMedCrossRefGoogle Scholar
  141. Thapar, A., and McGuffin, P. (1996). Genetic influences on life events in childhood. Psychol Med, 26, 1675–1681.Google Scholar
  142. Thase, M. E. (2009). Neurobiological aspects of depression. In I. H. Gotlib & C. L. Hammen (Eds.), Handbook of Depression, 2nd Ed. (pp. 187–217). New York: Guildford.Google Scholar
  143. Theorell, T., and Karasek, R. A. (1996). Current issues relating to psychosocial job strain and cardiovascular disease research. J Occup Health Psychol, 1, 9–26.PubMedCrossRefGoogle Scholar
  144. Turner, R. J., and Wheaton, B. (1995). Checklist measurement of stressful life events. In S. Cohen, R. C. Kessler, & L. U. Gordon (Eds.), Measuring Stress (pp. 29–58). New York: Oxford University Press.Google Scholar
  145. Tyrka, A. R., Price, L. H., Gelernter, J., Schepker, C., Anderson, G. M. et al (2009). Interaction of childhood maltreatment with the corticotrophin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity. Biol Psychiatry, 66, 681–685.PubMedCrossRefGoogle Scholar
  146. Uher, R., and McGuffin, P. (2008). The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis. Mol Psychiatry, 13, 131–146.PubMedCrossRefGoogle Scholar
  147. Uher, R., and McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry, 15, 18–22.PubMedCrossRefGoogle Scholar
  148. Van Dyck, C. H., Malison, R. T., Staley, J. K., Jacobsen, L. K., Seibyl, J. P. et al (2004). Central serotonin transporter availability measures with [123I]β-CIT SPECT in relation to serotonin transporter genotype. Am J Psychiatry, 161, 525–531.PubMedCrossRefGoogle Scholar
  149. Wallace, A. J., Mann, J. I., Sutherland, W. H. F., Williams, S., Chisholm, A. et al (2000). Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change. Atherosclerosis, 152, 327–336.PubMedCrossRefGoogle Scholar
  150. Weder, N., Yang, B. Z., Douglas-Palumberi, H., Massey, J., Krystal, J. H. et al (2009). MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma. Biol Psychiatry, 65, 417–424.PubMedCrossRefGoogle Scholar
  151. Whale, R., Quested, D. J., Laver, D., Harrison, P. J., and Cowen, P. J. (2000). Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine. Psychopharmacology, 150, 120–122.PubMedCrossRefGoogle Scholar
  152. Wierzbicki, M. (1989). Twins’ responses to pleasant, unpleasant, and life events. J Genet Psychol, 150, 135–145.PubMedCrossRefGoogle Scholar
  153. Williams, R. B., Marchuk, D. A., Gadde, K. M., Barefoot, J. C., Grichnik, K. et al (2001). Central nervous system serotonin function and cardiovascular responses to stress. Psychosom Med, 63, 300–305.PubMedGoogle Scholar
  154. Williams, R. B., Marchuk, D. A., Siegler, I. C., Barefoot, J. C., Helms, M. J. et al (2008). Childhood socioeconomic status and serotonin transporter gene polymorphism enhance cardiovascular reactivity to mental stress. Psychosom Med, 70, 32–39.PubMedCrossRefGoogle Scholar
  155. Wu, T., Snieder, H., and de Geus, E. (in press). Genetic influences on cardiovascular stress reactivity. Neurosci Biobeh Rev Google Scholar
  156. Wust, S., Federenko, I., Hellhammer, D.H., and Kirschbaum, C. (2000). Genetic factors, perceived chronic stress, and the free cortisol response to awakening. Psychoneuroendocrinology, 25, 707–720.PubMedCrossRefGoogle Scholar
  157. Wust, S., van Rossum, E. F. C., Federenko, I. S., Koper, J. W., Kumsta, R. et al (2004). Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab, 89, 565–573.PubMedCrossRefGoogle Scholar
  158. Yu, S. F., Zhou, W. H., Jiang, K. Y., Gu, G. Z., and Wang, S. (2008). Job stress, gene polymorphism of beta2-AR, and prevalence of hypertension. Biomed Environ Sci, 21, 239–246.PubMedCrossRefGoogle Scholar
  159. Zhou, Z., Zhu, G., Hariri, A. R., Enoch, M.-A., Scott, D. et al (2008). Genetic variation in human NPY expression affects stress response and emotion. Nature, 452, 997–1002.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Behavioral Physiology Laboratory, Department of PsychologyUniversity of PittsburghPittsburghUSA
  2. 2.Weight Control and Diabetes Research Center, Brown Medical School and The Miriam HospitalProvidenceUSA

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