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Gene × Environment Interaction Models in Psychiatric Genetics

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Behavioral Neurogenetics

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 12))

Abstract

Gene–environment (G × E) interaction research is an emerging area in psychiatry, with the number of G × E studies growing rapidly in the past two decades. This article aims to give a comprehensive introduction to the field, with an emphasis on central theoretical and practical problems that are worth considering before conducting a G × E interaction study. On the theoretical side, we discuss two fundamental, but controversial questions about (1) the validity of statistical models for biological interaction and (2) the utility of G × E research for psychiatric genetics. On the practical side, we focus on study characteristics that potentially influence the outcome of G × E interaction studies and discuss strengths and pitfalls of different study designs, including recent approaches like Genome–Environment Wide Interaction Studies (GEWIS). Finally, we discuss recent developments in G × E interaction research on the most heavily investigated example in psychiatric genetics, the interaction between a serotonin transporter gene promoter variant (5-HTTLPR) and stress on depression.

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References

  • Abdolmaleky HM, Smith CL, Faraone SV, Shafa R, Stone W, Glatt SJ, Tsuang MT (2004) Methylomics in psychiatry: modulation of Gene-environment interactions may be through DNA methylation. Am J Med Genet B Neuropsychiatr Genet 127B(1):51–59. doi:10.1002/ajmg.b.20142

    Article  PubMed  Google Scholar 

  • Albert PS, Ratnasinghe D, Tangrea J, Wacholder S (2001) Limitations of the case-only design for identifying Gene-environment interactions. Am J Epidemiol 154(8):687–693

    Article  PubMed  CAS  Google Scholar 

  • Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch-Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jorgensen T, Pedersen O, Hansen T (2008) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57(1):95–101. doi:10.2337/db07-0910, db07-0910 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004) Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 55(7):733–738. doi:10.1016/j.biopsych.2003.12.008, S0006322304000046 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ (2008) Association of fkbp5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299(11):1291–1305. doi:10.1001/jama.299.11.1291, 299/11/1291 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M (2008) Interaction between crhr1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 63(2):146–151. doi:10.1016/j.biopsych.2007.04.026, S0006-3223(07)00375-7 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Bradley RG, Binder EB, Epstein MP, Tang Y, Nair HP, Liu W, Gillespie CF, Berg T, Evces M, Newport DJ, Stowe ZN, Heim CM, Nemeroff CB, Schwartz A, Cubells JF, Ressler KJ (2008) Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch Gen Psychiatry 65(2):190–200. doi:10.1001/archgenpsychiatry.2007.26

    Article  PubMed  CAS  Google Scholar 

  • Brookes KJ, Mill J, Guindalini C, Curran S, Xu X, Knight J, Chen CK, Huang YS, Sethna V, Taylor E, Chen W, Breen G, Asherson P (2006) A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch Gen Psychiatry 63(1):74–81. doi:10.1001/archpsyc.63.1.74, 63/1/74 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Brummett BH, Krystal AD, Ashley-Koch A, Kuhn CM, Zuchner S, Siegler IC, Barefoot JC, Ballard EL, Gwyther LP, Williams RB (2007) Sleep quality varies as a function of 5-HTTLPR genotype and stress. Psychosom Med 69(7):621–624. doi:10.1097/PSY.0b013e31814b8de6, PSY.0b013e31814b8de6 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Cardon LR, Palmer LJ (2003) Population stratification and spurious allelic association. Lancet 361(9357):598–604. doi:10.1016/S0140-6736(03)12520-2, S0140-6736(03)12520-2 [pii]

    Article  PubMed  Google Scholar 

  • Caspi A (1998) Personality development across the life course. In: Damon W, Eisenberg N (eds) Handbook of child psychology, vol 3. Wiley, New York, pp 311–388

    Google Scholar 

  • Caspi A, Moffitt TE (2006) Gene-environment interactions in psychiatry: joining forces with neuroscience. Nat Rev Neurosci 7(7):583–590. doi:10.1038/nrn1925, nrn1925 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297(5582):851–854. doi:10.1126/science.1072290, 297/5582/851 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389. doi:10.1126/science.1083968, 301/5631/386 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005) Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-o-methyltransferase gene: longitudinal evidence of a gene x environment interaction. Biol Psychiatry 57(10):1117–1127. doi:10.1016/j.biopsych.2005.01.026, S0006-3223(05)00103-4 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE (2010) Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 167(5):509–527. doi:10.1176/appi.ajp.2010.09101452

    Article  PubMed  Google Scholar 

  • Collins FS (2004) The case for a us prospective cohort study of genes and environment. Nature 429(6990):475–477. doi:10.1038/nature02628, nature02628 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Dempfle A, Scherag A, Hein R, Beckmann L, Chang-Claude J, Schafer H (2008) Gene-environment interactions for complex traits: definitions, methodological requirements and challenges. Eur J Hum Genet 16(10):1164–1172. doi:10.1038/ejhg.2008.106, ejhg2008106 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Eaton WW, Hall ALF, MacDonald R, McKibben J (2007) Case identification in psychiatric epidemiology: a review. Int Rev Psych 19(5):497–507. doi:10.1080/09540260701564906

    Article  Google Scholar 

  • Ewens WJ, Spielman RS (1995) The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet 57(2):455–464

    PubMed  CAS  Google Scholar 

  • Furman DJ, Hamilton JP, Joormann J, Gotlib IH (2010) Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR. Soc Cogn Affect Neurosci 6(3):270–276. doi:10.1093/scan/nsq029, nsq029 [pii]

    Google Scholar 

  • Gauderman WJ, Witte JS, Thomas DC (1999) Family-based association studies. J Natl Cancer Inst Monogr 26:31–37

    Article  PubMed  Google Scholar 

  • Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, Klein S, Grusser SM, Flor H, Schumann G, Mann K, Buchel C (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8(1):20–21. doi:10.1038/nn1366, nn1366 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Homberg JR, Olivier JD, Smits BM, Mul JD, Mudde J, Verheul M, Nieuwenhuizen OF, Cools AR, Ronken E, Cremers T, Schoffelmeer AN, Ellenbroek BA, Cuppen E (2007) Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system. Neuroscience 146(4):1662–1676. doi:10.1016/j.neuroscience.2007.03.030, S0306-4522(07)00343-0 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Hunter DJ (2005) Gene-environment interactions in human diseases. Nat Rev Genet 6(4):287–298. doi:10.1038/nrg1578

    Article  PubMed  CAS  Google Scholar 

  • Hunter DJ, Altshuler D, Rader DJ (2008) From darwin’s finches to canaries in the coal mine–mining the genome for new biology. N Engl J Med 358(26):2760–2763. doi:10.1056/NEJMp0804318, 358/26/2760 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Hutchison KE, McGeary J, Smolen A, Bryan A, Swift RM (2002a) The DRD4 vntr polymorphism moderates craving after alcohol consumption. Health Psychol 21(2):139–146

    Article  PubMed  Google Scholar 

  • Hutchison KE, LaChance H, Niaura R, Bryan A, Smolen A (2002b) The drd4 vntr polymorphism influences reactivity to smoking cues. J Abnorm Psychol 111(1):134–143

    Article  PubMed  Google Scholar 

  • Jaffee SR, Price TS (2007) Gene-environment correlations: a review of the evidence and implications for prevention of mental illness. Mol Psychiatry 12(5):432–442. doi:10.1038/sj.mp.4001950

    PubMed  CAS  Google Scholar 

  • Joormann J, Hertel PT, LeMoult J, Gotlib IH (2009) Training forgetting of negative material in depression. J Abnorm Psychol 118(1):34–43. doi:10.1037/a0013794, 2009-01738-017 [pii]

    Article  PubMed  Google Scholar 

  • Kahn RS, Khoury J, Nichols WC, Lanphear BP (2003) Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr 143(1):104–110. doi:10.1016/S0022-3476(03)00208-7, S0022-3476(03)00208-7 [pii]

    Article  PubMed  Google Scholar 

  • Karg K, Burmeister M, Shedden K, Sen S (2010) The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 12(8):786–792

    Google Scholar 

  • Kendler KS, Eaves LJ (1986) Models for the joint effect of genotype and environment on liability to psychiatric illness. Am J Psychiatry 143(3):279–289

    PubMed  CAS  Google Scholar 

  • Kendler KS, Gardner CO (2010) Interpretation of interactions: guide for the perplexed. Br J Psychiatry 197(3):170–171. doi:10.1192/bjp.bp.110.081331, 197/3/170 [pii]

    Article  PubMed  Google Scholar 

  • Khoury MJ, Flanders WD (1996) Nontraditional epidemiologic approaches in the analysis of Gene-environment interaction: case-control studies with no controls! Am J Epidemiol 144(3):207–213

    Article  PubMed  CAS  Google Scholar 

  • Khoury MJ, Wacholder S (2009) Invited commentary: from genome-wide association studies to Gene-environment-wide interaction studies-challenges and opportunities. Am J Epidemiol 169 (2):227–230; discussion 234–225. doi:10.1093/aje/kwn351, kwn351 [pii]

    Google Scholar 

  • Koenen KC, Saxe G, Purcell S, Smoller JW, Bartholomew D, Miller A, Hall E, Kaplow J, Bosquet M, Moulton S, Baldwin C (2005) Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry 10(12):1058–1059

    Article  PubMed  CAS  Google Scholar 

  • Kraft P, Yen YC, Stram DO, Morrison J, Gauderman WJ (2007) Exploiting Gene-environment interaction to detect genetic associations. Hum Hered 63(2):111–119. doi:10.1159/000099183, 000099183 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Laucht M, Skowronek MH, Becker K, Schmidt MH, Esser G, Schulze TG, Rietschel M (2007) Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Arch Gen Psychiatry 64(5):585–590. doi:10.1001/archpsyc.64.5.585, 64/5/585 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Mandelli L, Serretti A, Marino E, Pirovano A, Calati R, Colombo C (2006) Interaction between serotonin transporter gene, catechol-o-methyltransferase gene and stressful life events in mood disorders. Int J Neuropsychopharmacol 10(04):437–447. doi:10.1017/s1461145706006882

    Article  Google Scholar 

  • Manolio TA, Brooks LD, Collins FS (2008) A hapmap harvest of insights into the genetics of common disease. J Clin Invest 118(5):1590–1605. doi:10.1172/JCI34772

    Article  PubMed  CAS  Google Scholar 

  • McClelland GH, Judd CM (1993) Statistical difficulties of detecting interactions and moderator effects. Psychol Bull 114(2):376–390

    Article  PubMed  CAS  Google Scholar 

  • Merikangas KR, Risch N (2003) Will the genomics revolution revolutionize psychiatry? Am J Psychiatry 160(4):625–635

    Article  PubMed  Google Scholar 

  • Moffitt TE, Caspi A, Rutter M (2005) Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry 62(5):473–481. doi:10.1001/archpsyc.62.5.473, 62/5/473 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Moffitt TE, Caspi A, Rutter M (2006) Measured Gene-environment interactions in psychopathology: concepts, research strategies, and implications for research, intervention, and public understanding of genetics. Perspect Psychol Sci 1(1):5–27

    Article  Google Scholar 

  • Monroe SM (2008) Modern approaches to conceptualizing and measuring human life stress. Annu Rev Clin Psychol 4:33–52. doi:10.1146/annurev.clinpsy.4.022007.141207

    Article  PubMed  Google Scholar 

  • Munafo MR, Durrant C, Lewis G, Flint J (2009) Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 65(3):211–219. doi:10.1016/j.biopsych.2008.06.009, S0006-3223(08)00731-2 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Nuevo R, Lehtinen V, Reyna-Liberato PM, Ayuso-Mateos JL (2009) Usefulness of the beck depression inventory as a screening method for depression among the general population of finland. Scand J Public Health 37(1):28–34. doi:10.1177/1403494808097169, 37/1/28 [pii]

    Article  PubMed  Google Scholar 

  • Olsson CA, Byrnes GB, Lotfi-Miri M, Collins V, Williamson R, Patton C, Anney RJL (2005) Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health. Mol Psychiatry 10(9):868–876

    Article  PubMed  CAS  Google Scholar 

  • Onkamo P, Toivonen H (2006) A survey of data mining methods for linkage disequilibrium mapping. Hum Genomics 2(5):336–340

    PubMed  CAS  Google Scholar 

  • Ottman R (1990) An epidemiologic approach to Gene-environment interaction. Genet Epidemiol 7(3):177–185. doi:10.1002/gepi.1370070302

    Article  PubMed  CAS  Google Scholar 

  • Ottman R (1994) Epidemiologic analysis of Gene-environment interaction in twins. Genet Epidemiol 11(1):75–86. doi:10.1002/gepi.1370110108

    Article  PubMed  CAS  Google Scholar 

  • Ozer EJ, Best SR, Lipsey TL, Weiss DS (2003) Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 129(1):52–73

    Article  PubMed  Google Scholar 

  • Pacheco J, Beevers CG, Benavides C, McGeary J, Stice E, Schnyer DM (2009) Frontal-limbic white matter pathway associations with the serotonin transporter gene promoter region (5-HTTLPR) polymorphism. J Neurosci 29(19):6229–6233. doi:10.1523/JNEUROSCI.0896-09.2009, 29/19/6229 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8(6):828–834. doi:10.1038/nn1463, nn1463 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Piegorsch WW, Weinberg CR, Taylor JA (1994) Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies. Stat Med 13(2):153–162

    Article  PubMed  CAS  Google Scholar 

  • Plomin R, DeFries JC, Loehlin JC (1977) Genotype-environment interaction and correlation in the analysis of human behavior. Psychol Bull 84(2):309–322

    Article  PubMed  CAS  Google Scholar 

  • Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301(23):2462–2471. doi:10.1001/jama.2009.878

    Article  PubMed  CAS  Google Scholar 

  • Roy A, Hu XZ, Janal MN, Goldman D (2007) Interaction between childhood trauma and serotonin transporter gene variation in suicide. Neuropsychopharmacology 32(9):2046–2052. doi:10.1038/sj.npp.1301331, 1301331 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Rutter M (2002) The interplay of nature, nurture, and developmental influences: the challenge ahead for mental health. Arch Gen Psychiatry 59(11):996–1000. ysa21000 [pii]

    Article  PubMed  Google Scholar 

  • Rutter M, Silberg J (2002) Gene-environment interplay in relation to emotional and behavioral disturbance. Annu Rev Psychol 53:463–490. doi:10.1146/annurev.psych.53.100901.135223, 53/1/463 [pii]

    Article  PubMed  Google Scholar 

  • Rutter M, Moffitt TE, Caspi A (2006) Gene-environment interplay and psychopathology: multiple varieties but real effects. J Child Psychol Psychiatry 47(3–4):226–261. doi:10.1002/da.20641

    Article  PubMed  Google Scholar 

  • Rutter M, Thapar A, Pickles A (2009) Gene-environment interactions: biologically valid pathway or artifact? Arch Gen Psychiatry 66(12):1287–1289. doi:10.1001/archgenpsychiatry.2009.167, 66/12/1287 [pii]

    Article  PubMed  Google Scholar 

  • Scarr S (1992) Developmental theories for the 1990s: development and individual differences. Child Dev 63(1):1–19

    Article  PubMed  CAS  Google Scholar 

  • Schaid DJ (1999) Case-parents design for Gene-environment interaction. Genet Epidemiol 16(3):261–273. doi:10.1002/(SICI)1098-2272(1999)16:3<261:AID-GEPI3>3.0.CO;2-M, 10.1002/(SICI)1098-2272(1999)16:3<261::AID-GEPI3>3.0.CO;2-M [pii]

    Article  PubMed  CAS  Google Scholar 

  • Schwarz N, Clore GL (1983) Mood, misattribution, and judgments of well-being: informative and directive functions of affective states. J Pers Soc Psychol 45(3):513–523. doi:10.1037/0022-3514.45.3.513

    Article  Google Scholar 

  • Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH (2005) Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet 37(4):435–440. doi:10.1038/ng1533, ng1533 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Seeger G, Schloss P, Schmidt MH, Ruter-Jungfleisch A, Henn FA (2004) Gene-environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism. Neurosci Lett 366(3):282–286. doi:10.1016/j.neulet.2004.05.049, S0304394004006305 [pii]

    Google Scholar 

  • Silva PA (1990) The dunedin multidisciplinary health and development study: a 15 year longitudinal study. Paediatr Perinat Epidemiol 4(1):76–107

    Article  PubMed  CAS  Google Scholar 

  • Sonuga-Barke EJ, Oades RD, Psychogiou L, Chen W, Franke B, Buitelaar J, Banaschewski T, Ebstein RP, Gil M, Anney R, Miranda A, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Thompson M, Asherson P, Faraone SV (2009) Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attention deficit/hyperactivity disorder. J Child Psychol Psychiatry 50(9):1052–1063. doi:10.1111/j.1469-7610.2009.02095.x, JCPP2095 [pii]

    Article  PubMed  Google Scholar 

  • Spinelli S, Schwandt ML, Lindell SG, Newman TK, Heilig M, Suomi SJ, Higley JD, Goldman D, Barr CS (2007) Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm. Dev Psychopathol 19(4):977–987. doi:10.1017/S095457940700048X, S095457940700048X [pii]

    Article  PubMed  Google Scholar 

  • Stein MB, Schork NJ, Gelernter J (2008) Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsychopharmacology 33(2):312–319. doi:10.1038/sj.npp.1301422, 1301422 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Stevens SE, Kumsta R, Kreppner JM, Brookes KJ, Rutter M, Sonuga-Barke EJ (2009) Dopamine transporter gene polymorphism moderates the effects of severe deprivation on adhd symptoms: developmental continuities in gene-environment interplay. Am J Med Genet B Neuropsychiatr Genet 150B(6):753–761. doi:10.1002/ajmg.b.31010

    Article  PubMed  CAS  Google Scholar 

  • Thapar A, Langley K, Fowler T, Rice F, Turic D, Whittinger N, Aggleton J, Van den Bree M, Owen M, O’Donovan M (2005) Catechol o-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 62(11):1275–1278. doi:10.1001/archpsyc.62.11.1275, 62/11/1275 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Thomas D (2010) Gene-environment-wide association studies: emerging approaches. Nat Rev Genet 11(4):259–272. doi:10.1038/nrg2764, nrg2764 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Thompson WD (1991) Effect modification and the limits of biological inference from epidemiologic data. J Clin Epidemiol 44(3):221–232. 0895-4356(91)90033-6 [pii]

    Article  PubMed  CAS  Google Scholar 

  • Uher R, McGuffin P (2007) The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis. Mol Psychiatry 13(2):131–146. doi:10.1038/sj.mp.4002067

    Article  PubMed  Google Scholar 

  • Uher R, McGuffin P (2010) The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry 15(1):18–22. doi:10.1038/mp.2009.123, mp2009123 [pii]

    Article  PubMed  CAS  Google Scholar 

  • van Os J, Rutten BP, Poulton R (2008) Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr Bull 34(6):1066–1082. doi:10.1093/schbul/sbn117

    Article  PubMed  Google Scholar 

  • van Winkel R, Henquet C, Rosa A, Papiol S, Faňanás L, De Hert M, Peuskens J, van Os J, Myin-Germeys I (2008) Evidence that the COMTVal158Met polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. Am J Med Genet Part B: Neuropsychiatr Genet 147B(1):10–17. doi:10.1002/ajmg.b.30559

    Article  Google Scholar 

  • Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96(6):434–442

    Article  PubMed  Google Scholar 

  • Witte JS, Gauderman WJ, Thomas DC (1999) Asymptotic bias and efficiency in case-control studies of candidate genes and Gene-environment interactions: basic family designs. Am J Epidemiol 149(8):693–705

    Article  PubMed  CAS  Google Scholar 

  • Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Brady K, Weiss RD, Farrer L, Gelernter J (2009) Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch Gen Psychiatry 66(11):1201–1209. doi:10.1001/archgenpsychiatry.2009.153, 66/11/1201 [pii]

    Article  PubMed  Google Scholar 

  • Yang Q, Khoury MJ (1997) Evolving methods in genetic epidemiology III. Gene-environment interaction in epidemiologic research. Epidemiol Rev 19(1):33–43

    Article  PubMed  CAS  Google Scholar 

  • Zammit S, Wiles N, Lewis G (2010a) The study of gene-environment interactions in psychiatry: limited gains at a substantial cost? Psychol Med 40:711–716. doi:10.1017/S0033291709991280

    Article  Google Scholar 

  • Zammit S, Owen MJ, Lewis G (2010b) Misconceptions about Gene-environment interactions in psychiatry. Evid Based Ment Health 13(3):65–68. doi:10.1136/ebmh.13.3.65, 13/3/65 [pii]

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. University of Michigan, Ann Arbor, MI, USA

    Katja Karg & Srijan Sen

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  1. Katja Karg
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  2. Srijan Sen
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Correspondence to Srijan Sen .

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Editors and Affiliations

  1. , Dep of Pharmacology and Therapeutics, School of Pharmacy, College Rd, Cork, 30, Ireland

    John F. Cryan

  2. , Department of Psychiatry and Psychothera, University of Würzburg, Füchsleinstrasse 15, Würzburg, 97080, Germany

    Andreas Reif

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Karg, K., Sen, S. (2011). Gene × Environment Interaction Models in Psychiatric Genetics. In: Cryan, J., Reif, A. (eds) Behavioral Neurogenetics. Current Topics in Behavioral Neurosciences, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_184

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