Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-30T15:02:26.782Z Has data issue: false hasContentIssue false
  • English
  • Français

The contribution of gene–environment interaction to psychopathology

Published online by Cambridge University Press:  11 October 2007

Anita Thapar ,
Gordon Harold ,
Frances Rice ,
Kate Langley  and
Michael O'Donovan
Anita Thapar*
Affiliation:
Cardiff University
Gordon Harold
Affiliation:
Cardiff University
Frances Rice
Affiliation:
Cardiff University
Kate Langley
Affiliation:
Cardiff University
Michael O'Donovan
Affiliation:
Cardiff University
*
Address correspondence and reprint requests to: Anita Thapar, Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

The study of gene–environment interaction (G × E) constitutes an area of significant social and clinical significance. Different types of research study designs are being used to investigate the contribution of G × E to psychopathology, although the term G × E has also been used and interpreted in different ways. Despite mixed evidence that G × E contributes to psychopathology, some promising and consistent findings are emerging. Evidence is reviewed in relation to depression, antisocial behavior, schizophrenia, and attention-deficit/hyperactivity disorder. Although findings from various research designs have different meaning, interestingly much of the evidence with regard to the contribution of G × E that has arisen from twin and adoption studies has been for antisocial behavior and depression. It is for these same forms of psychopathology that molecular genetic evidence of G × E has also been most convincing. Finally, current and anticipated methodological challenges and implications for future research in this area are considered.

Type
Research Article
Information
Development and Psychopathology , Volume 19 , Issue 4 , Fall 2007 , pp. 989 - 1004
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Altshuler, D., & Clark, A. G. (2005). Harvesting medical information from the human family tree. Science, 307, 1052–1053.CrossRefGoogle ScholarPubMed
Barkley, R. A., Karlsson, J., Pollard, S., & Murphy, J. V. (1985). Developmental changes in the mother–child interactions of hyperactive boys: Effects of two dose levels of Ritalin. Journal of Child Psychology and Psychiatry, 26, 705–715.CrossRefGoogle ScholarPubMed
Bell, R. Q. (1968). A reinterpretation of the direction of effects in studies of socialization. Psychological Review, 75, 81–85.CrossRefGoogle ScholarPubMed
Bhutta, A. T., Cleves, M. A., Casey, P. H., Cradock, M. M., & Anand, K. J. (2002). Cognitive and behavioral outcomes of school-aged children who were born preterm: A meta-analysis. Journal of the American Medical Association, 288, 728–737.CrossRefGoogle ScholarPubMed
Brookes, K. J., Mill, J., Guindalini, C., Curran, S., Xu, X., Knight, J., et al. (2006). A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Archives of General Psychiatry, 63, 74–81.CrossRefGoogle ScholarPubMed
Brookes, K. J., Neale, B., Xu, X., Thapar, A., Gill, M., Langley, K., et al. (2007). Differential dopamine receptor D4 allele association with ADHD dependent of proband season of birth. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.Google Scholar
Brunner, H. G., Nelen, M., Breakfield, X. O., Ropers, H. H., & Van Oost, B. A. (1993). Abnormal behaviour associated with a point mutation in the structural gene for monoamine oxidase A. Science, 262, 578–580.CrossRefGoogle Scholar
Button, T. M., Scourfield, J., Martin, N., Purcell, S., & McGuffin, P. (2005). Family dysfunction interacts with genes in the causation of antisocial symptoms. Behavior Genetics, 35, 115–120.CrossRefGoogle ScholarPubMed
Cadoret, R. J., Cain, C. A., & Crowe, R. R. (1983). Evidence for gene–environment interaction in the development of adolescent antisocial behavior. Behavior Genetics, 13, 301–310.CrossRefGoogle ScholarPubMed
Caspi, A., Langely, K., Craig, I., Milne, B., Moffit, T. E., O'Donovan, M., et al. (in press). A replicated molecular basis for subtyping antisocial behavior in ADHD. Archives of General Psychiatry.Google Scholar
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., et al. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851–854.CrossRefGoogle ScholarPubMed
Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., et al. (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 × Environment interaction. Biological Psychiatry, 57, 1117–1127.CrossRefGoogle Scholar
Chatterjee, N., Kalaylioglu, Z., Moslehi, R., Peters, U., & Wacholder, S. (2006). Powerful multilocus tests of genetic association in the presence of gene–gene and gene–environment interactions. The American Journal of Human Genetics, 79, 1002–1017.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Blender, J. (2004). A multiple-levels-of-analysis approach to the study of developmental processes in maltreated children. Proceedings of the National Academy of Sciences of the USA, 101, 17325–17326.CrossRefGoogle Scholar
Cicchetti, D., & Blender, J. (2006). A multiple-levels-of-analysis perspective on resilience. Implications for the developing brain, neural plasticity and preventive interventions. Proceedings of the National Academy of Sciences of the USA, 1094, 248–258.Google ScholarPubMed
Couzin, J., & Kaiser, J. (2007). Genomic hunt captures “diabetes DNA.” Science, 316, 820–822.CrossRefGoogle Scholar
Dannlowski, U., Ohrmann, P., Bauer, J., Deckert, J., Hohoff, C., Kugel, H., et al. (2007). 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology.Google ScholarPubMed
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of Biomedical Research, Saxena, R., Voight, B.F., Lyssenko, V., et al. (2007). Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science, 316, 1331–1336.CrossRefGoogle ScholarPubMed
Dizier, M. H., Bouzigon, E., Guilloud-Bataille, M., Siroux, V., Lemainque, A., Boland, A., et al. (2007). Evidence for Gene×Smoking Exposure interactions in a genome-wide linkage screen of asthma and bronchial hyper-responsiveness in EGEA families. European Journal of Human Genetics, 11.Google Scholar
Eaves, L., Silberg, J., & Erkanli, A. (2003). Resolving multiple epigenetic pathways to adolescent depression. Journal of Child Psychology and Psychiatry, 44, 1006–1014.CrossRefGoogle ScholarPubMed
Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., et al. (2004). Gene–environment interaction analysis of seretonin system markers with adolescent depression. Molecular Psychiatry, 9, 908–915.CrossRefGoogle Scholar
El-Faddagh, M., Laucht, M., Maras, A., Vohringer, L., & Schmidt, M. H. (2004). Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: A longitudinal study from birth to 11 years of age. Journal of Neural Transmitters, 111, 883–889.Google Scholar
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., et al. (2005). Molecular genetics of attention deficit/hyperactivity. Biological Psychiatry, 57, 1313–1323.CrossRefGoogle ScholarPubMed
Feinberg, M. E., Button, T. M., Neiderhiser, J. M., Reiss, D., & Hetherington, E. M. (2007). Parenting and adolescent antisocial behavior and depression: Evidence of Genotype × Parenting Environment interaction. Archives of General Psychiatry, 64, 457–465.CrossRefGoogle ScholarPubMed
Foley, D. L., Eaves, L. J., Wormley, B., Silberg, J. L., Maes, H. H., Kuhn, J., et al. (2004). Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Archives of General Psychiatry, 61, 738–744.CrossRefGoogle ScholarPubMed
Ge, X., Conger, R. D., Cadoret, R. J., Neiderhiser, J. M., Yates, W., Troughton, E., et al. (1996). The developmental interface between nature and nurture: A mutual influence model of child antisocial behavior and parent behaviors. Developmental Psychology, 32, 574–589.CrossRefGoogle Scholar
Haberstick, B. C., Lessen, J. M., Hopfer, C. J., Smolen, A., Ehringer, M. A., Timberlake, D., et al. (2005). Monoamine oxidase A (MAOA) and antisocial behaviours in the presence of childhood and adolescent maltreatment. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 135B, 59–64.CrossRefGoogle ScholarPubMed
Haiman, C. A., Patterson, N., Freedman, M. L., Myers, S. R., Pike, M. C., Waliszewska, A., et al. (2007). Multiple regions within 8q24 independently affect risk for prostate cancer. Nature & Genetics, 39, 638–644.CrossRefGoogle ScholarPubMed
Hariri, A. R., Drabant, E. M., Munoz, K. E., Kolachana, B. S., Mattay, V. S., Egan, M. F., et al. (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry, 622, 146–152.CrossRefGoogle Scholar
Hariri, A. R., Mattay, V. S., Tessitore, A., Fera, F., Smith, W. G., & Weinberger, D. R. (2005). Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology, 27, 1036–1040.CrossRefGoogle Scholar
Henquet, C., Murray, R., Linszen, D., & van Os, J. (2005). The environment and schizophrenia: The role of cannabis use. Schizophrenia Bulletin, 31, 608–612.CrossRefGoogle ScholarPubMed
Henquet, C., Rosa, A., Krabbendam, L., Papiol, S., Fananas, L., Drukker, M., et al. (2006). An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology, 31, 2748–2757.CrossRefGoogle ScholarPubMed
Huizinga, D., Haberstick, B. C., Smolen, A., Menard, S., Young, S. E., & Corley, R. P. (2006). Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype. Biological Psychiatry, 60, 677–683.CrossRefGoogle ScholarPubMed
Hultman, C. M., Torrang, A., Tuvblad, C., Cnattingius, S., Larsson, J. O., & Lichtenstein, P. (2007). Birth weight and attention-deficit/hyperactivity symptoms in childhood and early adolescence: A prospective Swedish twin study. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 370–377.CrossRefGoogle ScholarPubMed
Institute of Medicine Board on Health Sciences Policy. (2006). Genes, behavior and the social environment: Moving beyond the nature nurture debate. Washington, DC: National Academies Press.Google Scholar
Jabbi, M., Korf, J., Kema, I. P., Hartman, C., van der Pompe, G., Minderaa, R. B., et al. (2007). Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA. Molecular Psychiatry, 12, 83–90.CrossRefGoogle ScholarPubMed
Jaffee, S. R., Caspi, A., Moffitt, T. E., Dodge, K. A., Rutter, M., Taylor, A., et al. (2005). Nature×Nurture: Genetic vulnerabilities interact with physical maltreatment to promote conduct problems. Development and Psychopathology, 17, 67–84.CrossRefGoogle Scholar
Jaffee, S. R., Caspi, A., Moffitt, T. E., Polo-Tomas, M., Price, T. S., & Taylor, A. (2004). The limits of child effects: Evidence for genetically mediated child effects on corporal punishment but not on physical maltreatment. Developmental Psychology, 40, 1047–1058.CrossRefGoogle Scholar
Jaffee, S. R., & Price, T. S. (2007). Gene–environment correlations: A review of the evidence and implications for prevention of mental illness. Molecular Psychiatry, 12, 1432–1442.CrossRefGoogle ScholarPubMed
Kahn, R. S., Khoury, J., Nichols, W. C., & Lanphear, B. P. (2003). Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive–impulsive, inattentive, and oppositional behaviors. Journal of Pediatrics, 143, 104–110.CrossRefGoogle ScholarPubMed
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., et al. (2006). Brain-derived neurotrophic factor–5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673–680.CrossRefGoogle ScholarPubMed
Kendler, K. S., Kessler, R. C., Walters, E. E., Mclean, C., Neal, M. C., Heath, A. C., et al. (1995). Stressful life events, genetic liability, and onset of an episode of major depression in women. American Journal of Psychiatry, 152, 833–842.Google ScholarPubMed
Kendler, K., Kuhn, J., Vittum, J., Prescott, C., & Riley, B. (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: A replication. Archives of General Psychiatry, 62, 529–535.CrossRefGoogle Scholar
Kim, J. M., Stewart, R., Kim, S. W., Yang, S. J., Shin, I. S., Kim, Y. H., et al. (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biological Psychiatry.CrossRefGoogle ScholarPubMed
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., et al. (2006). MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11, 903–913.CrossRefGoogle ScholarPubMed
Knopik, V. S., Heath, A. C., Jacob, T., Slutske, W. S., Bucholz, K. K., Madden, P. A., et al. (2006). Maternal alcohol use disorder and offspring ADHD: Disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine, 36, 1461–1471.CrossRefGoogle ScholarPubMed
Krabbendam, L., & van Os, J. (2005). Schizophrenia and urbanicity: A major environmental influence—Conditional on genetic risk. Schizophrenia Bulletin, 31, 795–799.CrossRefGoogle Scholar
Kraft, P., Yen, Y. C., Stram, D. O., Morrison, J., & Gauderman, W. J. (2007). Exploiting gene–environment interaction to detect genetic associations. Human Heredity, 63,111–119.CrossRefGoogle ScholarPubMed
Langley, K., Rice, F., van den Bree, M. B., & Thapar, A. (2005). Maternal smoking during pregnancy as an environmental risk factor for attention deficit hyperactivity disorder behaviour. A review. Minerva Pediatrics, 57, 359–371.Google ScholarPubMed
Langley, K., Turic, D., Rice, F., Holmans, P., Van den Bree, M., Craddock, N., et al. (in press). Testing for Gene environment interaction effects in attention deficit hyperactivity disorder and associated antisocial behavior. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.Google Scholar
Laucht, M., Skowronek, M. H., Becker, K., Schmidt, M. H., Esser, G., Schulze, T. G., et al. (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. Archives of General Psychiatry, 64, 585–590.CrossRefGoogle ScholarPubMed
Lehn, H., Derks, E. M., Hudziak, J. J., Heutink, P., van Beijsterveldt, T. C., & Boomsma, D. I. (2007). Attention problems and attention-deficit/hyperactivity disorder in discordant and concordant monozygotic twins: Evidence of environmental mediators. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 83–91.CrossRefGoogle ScholarPubMed
McGuffin, P., Owen, M. J., & Gottesman, I. I. (Eds.). (2002). Psychiatric genetics and genomics. Oxford: Oxford University Press.CrossRefGoogle Scholar
Michelson, D., Read, H. A., Ruff, D. D., Witcher, J., Zhang, S., & McCracken, J. (2007). CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 242–251.CrossRefGoogle ScholarPubMed
Mill, J., Caspi, A., Williams, B. S., Craig, I., Taylor, A., Polo-Tomas, M., Berridge, C. W., et al. (2006). Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder: Evidence from 2 birth cohorts. Archives of General Psychiatry, 63, 462–469.CrossRefGoogle ScholarPubMed
Moffitt, T. E., Caspi, A., & Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62, 473–481.CrossRefGoogle ScholarPubMed
Moffitt, T. E., Caspi, A., & Rutter, M. (2006). Measured gene–environment interactions in psychopathology: Concepts, research strategies, and implications for research, intervention, and public understanding of genetics. Perspectives on Psychological Science, 1, 5–27.CrossRefGoogle ScholarPubMed
Neuman, R. J., Lobos, E., Reich, W., Henderson, C. A., Sun, L. W., & Todd, R. D. (2007). Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biological Psychiatry, 61, 1320–1328.CrossRefGoogle Scholar
O'Connor, T. G., Deater-Deckard, K., Fulker, D., Rutter, M., & Plomin, R. (1998). Genotype–environment correlations in late childhood and early adolescence: Antisocial behavioral problems and coercive parenting. Developmental Psychology, 34, 970–981.CrossRefGoogle ScholarPubMed
Pezawas, L., Meyer-Lindberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., et al. (2005). 5-HTTPR polymorphism impacts human cingulate–amygdala interactions: A genetic susceptibility mechanism for depression. Nature Neuroscience, 8, 828–834.CrossRefGoogle Scholar
Plomin, R., DeFries, J. C., Craig, I. W., & McGuffin, P. (Eds.). (2003). Behavioral genetics in the postgenomic era. Washington, DC: APA Books.CrossRefGoogle ScholarPubMed
Polanczyk, G., Zeni, C., Genro, J. P., Guimaraes, A. P., Roman, T., Hutz, M. H., et al. (2007). Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 64, 218–224.CrossRefGoogle ScholarPubMed
Purcell, S. (2002). Variance components models for gene–environment interaction in twin analysis. Twin Research, 5, 554–571.CrossRefGoogle ScholarPubMed
Ramadas, R. A., Sadeghnejad, A., Karmaus, W., Arshad, S. H., Matthews, S., Huebner, M., et al. (2007). Interleukin-1R antagonist gene and pre-natal smoke exposure are associated with childhood asthma. European Respiratory Journal, 29, 502–508.CrossRefGoogle ScholarPubMed
Rice, F., Harold, G. T., Shelton, K. H., & Thapar, A. (2006). Family conflict interacts with genetic liability in predicting childhood and adolescent depression. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 841–848.CrossRefGoogle ScholarPubMed
Rice, F., Harold, G. T., & Thapar, A. (2003). Negative life events as an account of age related differences in the genetic aetiology of depression in childhood and adolescence. Journal of Child Psychology and Psychiatry, 44, 977–987.CrossRefGoogle ScholarPubMed
Rutter, M. (2006). Genes and behavior: Nature–nurture interplay explained. London: Blackwell.Google Scholar
Rutter, M. (2007). Gene–environment interdependence. Developmental Science, 10, 12–18.CrossRefGoogle ScholarPubMed
Rutter, M., Giller, H., & Hagell, A. (1998). Antisocial behaviour by young people. Cambridge: Cambridge University Press.Google Scholar
Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene–environment interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry, 47, 226–261.CrossRefGoogle ScholarPubMed
Rutter, M., Pickles, A., Murray, R., & Eaves, L. (2001). Testing hypotheses on specific environmental causal effects on behavior. Psychological Bulletin, 127, 291–324.CrossRefGoogle ScholarPubMed
Schachar, R., Taylor, E., Wieselberg, M., Thorley, G., & Rutter, M. (1987). Changes in family function and relationships in children who respond to methylphenidate. Journal of the American Academy of Child & Adolescent Psychiatry, 26, 728–732.CrossRefGoogle ScholarPubMed
Scheid, J. M., Holzman, C. B., Jones, N., Friderici, K. H., Nummy, K. A., Symonds, L. L., et al. (2007). Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype. Genes, Brain and Behavior, 6, 453–464.CrossRefGoogle ScholarPubMed
Schmidt, S., Qin, X., Schmidt, M. A., Martin, E. R., & Hauser, E. R. (2007). Interpreting analyses of continuous covariates in affected sibling pair linkage studies. Genetics and Epidemiology.CrossRefGoogle ScholarPubMed
Seeger, G., Schloss, P., Schmidt, M. H., Ruter-Jungfleisch, A., & Henn, F. A. (2004). Gene–environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism. Neuroscience Letters, 366, 282–286.CrossRefGoogle ScholarPubMed
Sengupta, S. M., Grizenko, N., Schmitz, N., Schwartz, G., Ben Amor, L., & Bellingham, J. (2006). COMT Val108/158Met gene variant, birth weight, and conduct disorder in children with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 1363–1369.CrossRefGoogle ScholarPubMed
Silberg, J., Pickles, A., Rutter, M., Hewitt, J., Simonoff, E., Maes, H., et al. (1999). The influence of genetic factors and life stress on depression among adolescent girls. Archives of General Psychiatry, 56, 225–232.CrossRefGoogle ScholarPubMed
Silberg, J., Rutter, M., Neale, M., & Eaves, L. (2001). Genetic moderation of environmental risk for depression and anxiety in adolescent girls. British Journal of Psychiatry, 179, 116–121.CrossRefGoogle ScholarPubMed
St. Clair, D., Xu, M., Wang, P., Yu, Y., Fang, Y., Zhang, F., et al. (2005). Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. Journal of the American Medical Association, 294, 557–562.CrossRefGoogle Scholar
Stein, M. B., Schork, N. J., & Gelernter, J. (in press). Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsy-chopharmacology.Google Scholar
Susser, E. S., & Lin, S. P. (1992). Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944–1945. Archives of General Psychiatry, 49, 983–988.CrossRefGoogle Scholar
Talmud, P., Flavell, D., Alfakih, K., Cooper, J., Balmforth, A., Sivananthan, M., et al. (2007). The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease. Clinical Science (London), 112, 617–624.CrossRefGoogle ScholarPubMed
Thapar, A., Holmes, J., Poulton, K., & Harrington, R. (1999). Genetic basis of attention deficit and hyperactivity. British Journal of Psychiatry, 174, 105–111.CrossRefGoogle ScholarPubMed
Thapar, A., Langley, K., Asherson, P., & Gill, M. (2007). Gene–environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective. British Journal of Psychiatry, 190, 1–3.CrossRefGoogle ScholarPubMed
Thapar, A., Langley, K., Owen, M., & O'Donovan, M. (in press). Advances in genetic findings on attention deficit hyperactivity disorder. Psychological Medicine.Google Scholar
Thapar, A., O'Donovan, M., & Owen, M. J. (2005). The genetics of attention deficit hyperactivity disorder. Human Molecular Genetics, 15, R275–R282.CrossRefGoogle Scholar
Thapar, A., & Rutter, M. (2007). Genetics. In Rutter, M., Bishop, D., Pine, D., Scott, S., Stevenson, J., Taylor, E., & Thapar, A. (Eds.), Textbook of child & adolescent psychiatry (5th ed.). Oxford: Blackwell.Google Scholar
Tienari, P., Wynne, L. C., Sorri, A., Lahti, I., Laksy, K., Moring, J., et al. (2004). Genotype–environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees. British Journal of Psychiatry, 184, 216–222.CrossRefGoogle ScholarPubMed
Tunbridge, E. M., Harrison, P. J., & Weinberger, D. R. (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry, 60, 141–151.CrossRefGoogle ScholarPubMed
Tuvblad, C., Grann, M., & Lichtenstein, P. (2006). Heritability for adolescent antisocial behavior differs with socioeconomic status: Gene–environment interaction. Journal of Child Psychology and Psychiatry, 47, 734–743.CrossRefGoogle ScholarPubMed
Vergne, D.E., & Nemeroff, C. B. (2006). The interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major depression. Current Psychiatry Reports, 8, 452–457.CrossRefGoogle ScholarPubMed
Wahlberg, K. E., Wynne, L. C., Oja, H., Keskitalo, P., Pykalainen, L., Lahti, I., et al. (1997). Gene–environment interaction in vulnerability to schizophrenia: Findings from the Finnish Adoptive Family Study of Schizophrenia. American Journal of Psychiatry, 154, 355–362.Google ScholarPubMed
Widom, C. S., & Brzustowicz, L. M. (2006). MAOA and the “cycle of violence”: Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological Psychiatry, 60, 684–689.CrossRefGoogle ScholarPubMed
Williams, H. J., Owen, M. J., & O'Donovan, M. C. (2007). Is COMT a susceptibility gene for schizophrenia? Schizophrenia Bulletin, 33, 635–641.CrossRefGoogle ScholarPubMed
Zalsman, G., Huang, Y. Y., Oquendo, M. A., Burke, A. K., Hu, X. Z., Brent, D. A., et al. (2006). Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. American Journal of Psychiatry, 163, 1588–1593.CrossRefGoogle ScholarPubMed
Zammit, S., & Owen, M. J. (2006). Stressful life events, 5-HTT genotype and risk of depression. British Journal of Psychiatry, 188, 199–201.CrossRefGoogle ScholarPubMed