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Gene x environment interactions as dynamical systems: clinical implications

  • Received: 29 October 2015 Accepted: 21 December 2015 Published: 28 December 2015
  • The etiology and progression of the chronic diseases that account for the highest rates of mortality in the US, namely, cardiovascular diseases and cancers, involve complex gene x environment interactions. Yet despite the general agreement in the medical community given to this concept, there is a widespread lack of clarity as to what the term ‘interaction’ actually means. The consequence is the use of linear statistical methods to describe processes that are biologically nonlinear, resulting in clinical applications that are often not optimal. Gene x environment interactions are characterized by dynamic, nonlinear molecular networks that change and evolve over time; and by emergent properties that cannot be deduced from the characteristics of their individual subcomponents. Given the nature of these systemic properties, reductionist methods are insufficient for fully providing the information relevant to improving therapeutic outcomes. The purpose of this article is to provide an overview of these concepts and their relevance to prevention and interventions.

    Citation: Sarah S. Knox. Gene x environment interactions as dynamical systems: clinical implications[J]. AIMS Molecular Science, 2016, 3(1): 1-11. doi: 10.3934/molsci.2016.1.1

    Related Papers:

  • The etiology and progression of the chronic diseases that account for the highest rates of mortality in the US, namely, cardiovascular diseases and cancers, involve complex gene x environment interactions. Yet despite the general agreement in the medical community given to this concept, there is a widespread lack of clarity as to what the term ‘interaction’ actually means. The consequence is the use of linear statistical methods to describe processes that are biologically nonlinear, resulting in clinical applications that are often not optimal. Gene x environment interactions are characterized by dynamic, nonlinear molecular networks that change and evolve over time; and by emergent properties that cannot be deduced from the characteristics of their individual subcomponents. Given the nature of these systemic properties, reductionist methods are insufficient for fully providing the information relevant to improving therapeutic outcomes. The purpose of this article is to provide an overview of these concepts and their relevance to prevention and interventions.


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    [1] Knox SS, Guo X, Zhang Y, et al. (2010) AGT M235T genotype /anxiety interaction and gender in the HyperGEN Study.PLoS One 5: E13353. doi: 10.1371/journal.pone.0013353
    [2] Colhoun HM, McKeigue PM, Smith GD (2003) Problems of reporting genetic associations with complex outcomes. Lancet 361: 865-872. doi: 10.1016/S0140-6736(03)12715-8
    [3] Munafo MR, Flint J (2004) Meta-analysis of genetic association studies.Trends Genet 20: 439-444. doi: 10.1016/j.tig.2004.06.014
    [4] Bissel MJ, LaBarge MA (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 7: 17-23.
    [5] Pedersen NL (1994) The nature and nurture of personality. In De Raad, Hofstee WKB, Van Heck GL (Eds.) Personality Psychology in Europe Tilburg University Press, 110-132.
    [6] Knox SS (2010) From ‘omics’ to complex disease: a systems biology approach to gene-environment interactions in cancer. Cancer Cell Int 10: 11.
    [7] Robbins CL, Hutchings Y, Dietz PM (2014) History of preterm birth and subsequent cardiovascular disease: a systematic review.AJOG 210: 285-297.
    [8] Plomin R (2011) Commentary: Why are children in the same family so different? Non-shared environment three decades later. Int J Epi 40: 582-592.
    [9] Burt CH (2015) Heritability studies: methodological flaws, invalidated dogmas, and changing paradigms. In Perry BL (ed.) Genetics, Health and Soc (Adv in Med Sociol), 1-44. Emerald Group Publishing Limited.
    [10] Burt CH, Simons RL (2015) Hertitability studies in the postgenomic era: the fatal flaw is conceptual.Criminology 53: 103-112.
    [11] Joseph J (2013) The use of the classical twin method in the social and behavioral sciences: the fallacy continues.J Mind Behav34: 1-40.
    [12] Stenberg A (2013) Interpreting estimates of heritability – A note on the twin decomposition.Econ Hum Biol 11: 201-205. doi: 10.1016/j.ehb.2012.05.002
    [13] Knox SS, Wilk JB, Zhang Y (2004) A genome scan for hostility: the national heart, lung, and blood institute family heart study. Mol Psychiatry 9: 124-127. doi: 10.1038/sj.mp.4001447
    [14] Hofseth LJ, Hussain SP, Harris CC (2004) P53: 25 years after its discovery. Trends Pharmacol Sci 25: 177-181. doi: 10.1016/j.tips.2004.02.009
    [15] Hainaut P, Wiman KG (2009) 30 years and a long way into p53 research. Lancet Oncol 10: 913-919.
    [16] Parihar A, Eubank TD,Doseff A (2010) Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death.J Innate Immun 2: 204-215. doi: 10.1159/000296507
    [17] Cohen IR, Harel D (2007) Explaining a complex living system: dynamics, multi-scaling and emergence.JR Soc Interface 4: 175-182. doi: 10.1098/rsif.2006.0173
    [18] Gibson DG, Glass JI, Lartigue C, et al. (2010) Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329: 38-39. doi: 10.1126/science.1193749
    [19] MacNeil LT, Walhout AJM (2011) Gene regulatory networks and the role of robustness in stochasticity in the control of gene expression. Genome Res 21: 645-657. doi: 10.1101/gr.097378.109
    [20] Barabasi AL, Albert R (1999) Emergence of scaling in random networks. Science 286: 509-512.
    [21] Albert R (2005) Scale-free networks in cell biology. J Cell Sci 118: 4947-4957.
    [22] Kruse J, Gu W (2009) Modes of p53 regulation. Cell 137: 609-622. doi: 10.1016/j.cell.2009.04.050
    [23] Riley T, Sontag E, Chen P, et al. (2008) Transcriptional control of human p53 regulated genes.Nat Rev Mol Cell Biol 9: 402-412. doi: 10.1038/nrm2395
    [24] Hein O, Schwind M, Konig W (2006) Scale-free networks. The impact of fat tailed degree distribution on diffusion and communication processes.Wirschftsinformatik 48: 267-275.
    [25] Zhou L, Aon MA, Almas T, et al. (2010) A reaction-diffusion model of ROS-induced ROS release in a mitochondrial network. PLOS Comp Biol 6: e1000657. doi: 10.1371/journal.pcbi.1000657
    [26] Larremore, DB, Shew WL, Restrepo JG (2011) Predicting criticality and dynamic range in complex networks: effects of topology. Phys Rev Let 106: 1580101.
    [27] Nykter M, Price ND, Aldana M, et al. (2008) Gene expression dynamics in macrophage exhibit criticality. Proc Natl Acad Sci U S A 105: 1897-1900. doi: 10.1073/pnas.0711525105
    [28] Ito K, Gunji YP (1994) Self-organization of living systems towards criticality at the edge of chaos. Biosystems 33: 17-24. doi: 10.1016/0303-2647(94)90057-4
    [29] MacArthur BD, Sanchez-Garcia RJ, Ma’ayan A (2010) Microdynamics and criticality of adaptive regulatory networks. Phys Rev Let 104: 168701. doi: 10.1103/PhysRevLett.104.168701
    [30] Seeman TE, Singer BH, Rowe JW (1997) Price of adaption-allostatic load and its health consequences. MacArthur Studies of Successful Aging. Arch Intern Med 157: 2259-2268.
    [31] McEwen BS (1998) Stress, adaption, and disease: Allostasis and allostatic load. Ann NY Acad Sci 840: 33-44. doi: 10.1111/j.1749-6632.1998.tb09546.x
    [32] Picard M, Juster RP, McEwen BS (2014) Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids. Nat Rev Endocrinol 10: 303-310. doi: 10.1038/nrendo.2014.22
    [33] Zalli A, Carvalho LA, Lin J, et al. (2014) Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources. Proc Natl Acad Sci U S A 111: 4519-4524. doi: 10.1073/pnas.1322145111
    [34] Dich N, Doan SN, Kivimaki M, et al. (2014) A non-linear association between self-reported negative emotional response to stress and subsequent allostatic load; Prospective results from the Whitehall II cohort study.Psychoneuroendocrinology 49: 54-61.
    [35] Knox SS, Basu S, Remick S (2014) A systems approach to cancer health disparities in Appalachia.Austin J Pub Health 1: 10.
    [36] Greaves M (2006) Infection, immune responses and the aetiology of childhood leukaemia. Nat RevCancer 6: 193-203. doi: 10.1038/nrc1816
    [37] Perez-Andreu V, Roberts KG, Harvey RC, et al. (2013) Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat Genet 12: 1491-1498.
    [38] Chaturvedi MM, Sung B, Yadav VR, et al. (2011) NF-κβ addiction and its role in cancer: ‘one size does not fit all’. Oncogene 30: 1615-1630. doi: 10.1038/onc.2010.566
    [39] Gudmundsdottir K, Tryggvadottir L, Eyfjord JE (2011) GSTM1, GSTT1, and GSTP1 genotypes in relation breast cancer risk and frequency of mutations in the p53 gene. Cancer Epi Biomark Prev 10: 1169-1173.
    [40] Joseph MA, Moysich KB, Freudenheim JL, et al. (2004) Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk.Nutr Cancer 50: 206-213. doi: 10.1207/s15327914nc5002_11
    [41] Kamb A, Wee S, Lengauer C (2007) Why is cancer drug discovery so Difficult? Nat Rev/Drug Discov 6: 115-120. doi: 10.1038/nrd2155
    [42] Kerkela R, Grazette L, Yacobi R, et al. (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12: 908-916. doi: 10.1038/nm1446
    [43] Ferber D (2006) Wonder drug may not be so wonderful.Science July 24.
    [44] Landier W, Bhatia S, Eshelman DA, et al. (2004) Development of risk-based guidelines for pediatric cancer survivors: The children’s oncology group long-term follow-up guidelines from the children’s oncology group late effects committee and nursing discipline. J Clin Oncol 22: 4979-4990. doi: 10.1200/JCO.2004.11.032
    [45] Global Burden of Disease: 2004 Update. World Health Organization 2008. ISBN 978 92 4 156371 0. Part 2, p. 10.
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