Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-05T04:04:50.014Z Has data issue: false hasContentIssue false

Behavior genetics: Past, present, future

Published online by Cambridge University Press:  17 December 2013

Sara R. Jaffee*
Affiliation:
University of Pennsylvania King's College London
Thomas S. Price
Affiliation:
University of Pennsylvania
Teresa M. Reyes
Affiliation:
University of Pennsylvania
*
Address correspondence and reprint requests to: Sara R. Jaffee, Department of Psychology, University of Pennsylvania, 3720 Walnut Street, Philadelphia, PA 19104; E-mail: [email protected].

Abstract

The disciplines of developmental psychopathology and behavior genetics are concerned with many of the same questions about the etiology and course of normal and abnormal behavior and about the factors that promote typical development despite the presence of risk. The goal of this paper is to summarize how research in behavior genetics has shed light on questions that are central to developmental psychopathology. We briefly review the origins of behavior genetics, summarize the findings that have been gleaned from several decades of quantitative and molecular genetics research, and describe future directions for research that will delineate gene function as well as pathways from genes to brain to behavior. The importance of environmental contributions, at both genetic and epigenetic levels, will be discussed. We conclude that behavior genetics has made significant contributions to developmental psychopathology by documenting the interplay among risk and protective factors at multiple levels of the organism, by clarifying the causal status of risk exposures, and by identifying factors that account for change and stability in psychopathology. As the tools to identify gene function become increasingly sophisticated, and as behavioral geneticists become increasingly interdisciplinary in their scope, the field is poised to make ever greater contributions to our understanding of typical and atypical development.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2013 

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

Alia-Klein, N., Goldstein, R. Z., Kriplani, A., Logan, J., Tomasi, D., Williams, B., et al. (2008). Brain monoamine oxidase A activity predicts trait aggression. Journal of Neuroscience, 28, 50995104.Google Scholar
Aschard, H., Lutz, S., Maus, B., Duell, E. J., Fingerlin, T. E., Chatterjee, N., et al. (2012). Challenges and opportunities in genome-wide environmental interaction (GWEI) studies. Human Genetics, 131, 15911613.Google Scholar
Aristotle. (1942). On the generation of animals (Peck, A. L., trans.). Cambridge, MA: Harvard University Press.Google Scholar
Atz, M., Walsh, D., Cartagena, P., Li, J., Evans, S., Choudary, P., et al. (2007). Methodological considerations for gene expression profiling of human brain. Journal of Neuroscience Methods, 163, 295309.Google Scholar
Baranzini, S. E., Mudge, J., van Velkinburgh, J. C., Khankhanian, P., Khrebtukova, I., Miller, N. A., et al. (2010). Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature, 464, 13511356.Google Scholar
Beam, C. R., & Turkheimer, E. (2013). Phenotype–environment correlations in longitudinal twin models. Development and Psychopathology, 25, 716.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908.Google Scholar
Berridge, K. C. (2007). The debate over dopamine's role in reward: The case for incentive salience. Psychopharmacology, 191, 391431.Google Scholar
Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting. Brain Research, 1380, 4277.CrossRefGoogle ScholarPubMed
Bick, J., Naumova, O., Hunter, S., Barbot, B., Lee, M., Luthar, S. S., et al. (2012). Childhood adversity and DNA methylation of genes involved in the hypothalamus–pituitary–adrenal axis and immune system: Whole-genome and candidate-gene associations. Development and Psychopathology, 24, 14171425.CrossRefGoogle ScholarPubMed
Biederman, J., Faraone, S., Milberger, S., Curtis, S., Chen, L., Marrs, A., et al. (1996). Predictors of persistence and remission of ADHD into adolescence: Results from a four-year prospective follow-up study. Journal of the American Academy of Child & Adolescent Psychiatry, 35, 343351.CrossRefGoogle ScholarPubMed
Bigos, K. L., & Weinberger, D. R. (2010). Imaging genetics—Days of future past. NeuroImage, 53, 804809.Google Scholar
Bishop, D. (2009). Genes, cognition, and communication: Insights from neurodevelopmental disorders. Annals of the New York Academy of Sciences, 1156, 115.CrossRefGoogle ScholarPubMed
Boardman, J. D. (2009). State-level moderation of genetic tendencies to smoke. American Journal of Public Health, 99, 480486.Google Scholar
Boardman, J. D., Saint Onge, J. M., Haberstick, B. C., Timberlake, D. S., & Hewitt, J. K. (2008). Do schools moderate the genetic determinants of smoking? Behavior Genetics, 38, 234246.CrossRefGoogle ScholarPubMed
Borghol, N., Suderman, M., McArdle, W., Racine, A., Hallett, M., Pembrey, M., et al. (2012). Associations with early-life socio-economic position in adult DNA methylation. International Journal of Epidemiology, 41, 6274.Google Scholar
Borkenau, P., Riemann, R., Angleitner, A., & Spinath, F. M. (2002). Similarity of childhood experiences and personality resemblance in monozygotic and dizygotic twins: A test of the equal environments assumption. Personality and Individual Differences, 33, 261269.Google Scholar
Buckholtz, J. W., Callicott, J. H., Kolachana, B., Hariri, A. R., Goldberg, T. E., Genderson, M., et al. (2008). Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular Psychiatry, 13, 313324.Google Scholar
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527.CrossRefGoogle 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, 851854.Google Scholar
Caspi, A., & Moffitt, T. E. (1995). The continuity of maladaptive behavior: From description to understanding in the study of antisocial behavior. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology (1st ed., pp. 472511). New York: Wiley.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H. et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 31, 386389.Google Scholar
Charney, E. (2012). Behavior genetics and postgenomics. Behavioral and Brain Sciences, 35, 331358.Google Scholar
Chen, E., Miller, G. E., Kobor, M. S., & Cole, S. W. (2011). Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood. Molecular Psychiatry, 16, 729737.Google Scholar
Chen, E., Miller, G. E., Walker, H. A., Arevalo, J. M., Sung, C. Y., & Cole, S. W. (2009). Genome-wide transcriptional profiling linked to social class in asthma. Thorax, 64, 3843.Google Scholar
Cheung, V. G., & Spielman, R. S. (2009). Genetics of human gene expression: Mapping DNA variants that influence gene expression. Nature Reviews Genetics, 10, 595604.Google Scholar
Cicchetti, D. (1984). The emergence of developmental psychopathology. Child Development, 55, 17.Google Scholar
Cicchetti, D. (1993). Developmental psychopathology: Reactions, reflections, projections. Developmental Review, 13, 471502.Google Scholar
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597600.Google Scholar
Cirulli, E. T., & Goldstein, D. B. (2010). Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nature Reviews Genetics, 11, 415425.CrossRefGoogle ScholarPubMed
Clarren, S. K., & Smith, D. W. (1978). Fetal alcohol syndrome. New England Journal of Medicine, 298, 10631067.CrossRefGoogle ScholarPubMed
Cole, S. W. (2012). Socioenvironmental effects on gene expression. In Kendler, K. S., Jaffee, S. R., & Romer, D. (Eds.), The dynamic genome and mental health: The role of genes and environments in youth development (pp. 195225). New York: Oxford University Press.Google Scholar
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007). Social regulation of gene expression in human leukocytes. Genome Biology, 8, R189.Google Scholar
Costa, P. T. Jr., & McCrae, R. R. (1992). Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) Manual. Odessa, FL: Psychological Assessment Resources.Google Scholar
Cronk, N. J., Slutske, W. S., Madden, P. A. F., Bucholz, K. K., Reich, W., & Heath, A. C. (2002). Emotional and behavioral problems among female twins: An evaluation of the equal environments assumption. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 829837.Google Scholar
Danese, A., Moffitt, T. E., Pariante, C. M., Ambler, A., Poulton, R., & Caspi, A. (2008). Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Archives of General Psychiatry, 65, 409416.Google Scholar
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences, 104, 13191324.CrossRefGoogle Scholar
Davies, G., Tenesa, A., Payton, A., Yang, J., Harris, S. E., Liewald, D., et al. (2011). Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry, 16, 9961005.Google Scholar
Davies, M. N., Volta, M., Pidsley, R., Lunnon, K., Dixit, A., Lovestone, S., et al. (2012). Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biology, 13, R43.Google Scholar
Dick, D. M., Rose, R. J., Viken, R. J., Kaprio, J., & Koskenvuo, M. (2001). Exploring gene–environment interactions: Socioregional moderation of alcohol use. Journal of Abnormal Psychology, 110, 625632.Google Scholar
Dick, D. M., Viken, R., Purcell, S., Kaprio, J., Pulkkinen, L., & Rose, R. J. (2007). Parental monitoring moderates the importance of genetic and environmental influences on adolescent smoking. Journal of Abnormal Psychology, 116, 213218.Google Scholar
DiLalla, L. F., & Gottesman, I. I. (1991). Biological and genetic contributions to violence: Widom's untold tale. Psychological Bulletin, 109, 125129.Google Scholar
Dohrenwend, B. P., Levav, I., Shrout, P. E., Schwartz, S., Naveh, G., Link, B. G., et al. (1992). Socioeconomic status and psychiatric disorders: The causation–selection issue. Science, 255, 946952.Google Scholar
Donnelly, P. (2008). Progress and challenges in genome-wide association studies in humans. Nature, 456, 728731.Google Scholar
D'Onofrio, B. M., Turkheimer, E., Emery, R. E., Maes, H. H., Silberg, J., & Eaves, L. J. (2007). A children of twins study of parental divorce and offspring psychopathology. Journal of Child Psychology and Psychiatry, 48, 667675.CrossRefGoogle ScholarPubMed
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049.CrossRefGoogle ScholarPubMed
Ehli, E. A., Abdellaoui, A., Hu, Y. S., Hottenga, J. J., Kattenberg, M., van Beijsterveldt, T., et al. (2012). De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on attention problems. European Journal of Human Genetics, 20, 10371043.Google Scholar
Essex, M. J., Boyce, W. T., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M. A., et al. (2013). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development, 84, 5875.CrossRefGoogle ScholarPubMed
Feuk, L., Carson, A. R., & Scherer, S. W. (2006). Structural variation in the human genome. Nature Reviews Genetics, 7, 8597.Google Scholar
Fisher, R. A. (1918). The correlation between relatives on the supposition of Mendelian inheritance. Transactions of the Royal Society of Edinburgh, 52, 399433.CrossRefGoogle Scholar
Flint, J., & Munafo, M. R. (2007). The endophenotype concept in psychiatric genetics. Psychological Medicine, 37, 163180.Google Scholar
Fontaine, N. M. G., Rijsdijk, F. V., McCrory, E. J. P., & Viding, E. (2010). Etiology of different developmental trajectories of callous–unemotional traits. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 656664.Google Scholar
Fu, N., Drinnenberg, I., Kelso, J., Wu, J. R., Paabo, S., Zeng, R., et al. (2007). Comparison of protein and mRNA expression evolution in humans and chimpanzees. PloS ONE, 2, e216.Google Scholar
Galton, F. (1869). Hereditary genius: An inquiry into its laws and consequences. London: Macmillan & Co.CrossRefGoogle Scholar
Gibson, G. (2012). Rare and common variants: Twenty arguments. Nature Reviews Genetics, 13, 135145.Google Scholar
Goddard, G. H. M., & Lewis, C. M. (2010). Risk categorization for complex disorders according to genotype relative risk and precision in parameter estimates. Genetic Epidemiology, 34, 624632.Google Scholar
Happé, F. G. E. (1995). The role of age and verbal ability in the theory of mind task performance of subjects with autism. Child Development, 66, 843855.Google Scholar
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science, 297, 400403.CrossRefGoogle ScholarPubMed
Harkness, U. F., & Crombleholme, T. M. (2005). Twin–twin transfusion syndrome: Where do we go from here? Seminars in Perinatology, 29, 296304.CrossRefGoogle Scholar
Heijmans, B. T., & Mill, J. (2012). Commentary: The seven plagues of epigenetic epidemiology. International Journal of Epidemiology, 41, 7478.CrossRefGoogle ScholarPubMed
Hicks, B. M., Johnson, W., Durbin, C. E., Blonigen, D. M., Iacono, W. G., & McGue, M. (2013). Gene–environment correlation in the development of adolescent substance abuse: Selection effects of child personality and mediation via contextual risk factors. Development and Psychopathology, 25, 119132.Google Scholar
Hicks, B. M., South, S. C., DiRago, A. C., Iacono, W. G., & McGue, M. (2009). Environmental adversity and increasing genetic risk for externalizing disorders. Archives of General Psychiatry, 66, 640648.Google Scholar
Hugot, J. P., Chamaillard, M., Zouali, H., Lesage, S., Cezard, J. P., Belaiche, J., et al. (2001). Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature, 411, 599603.Google Scholar
Huizink, A. C., & Mulder, E. J. H. (2006). Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neuroscience & Biobehavioral Reviews, 30, 2441.Google Scholar
Jaenisch, R., & Bird, A. (2003). Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nature Genetics, 33, 245254.Google Scholar
Jaffee, S. R. (2002). Pathways to adversity in young adulthood among early childbearers. Journal of Family Psychology, 16, 3849.Google Scholar
Jaffee, S. R. (2012). Teasing out the role of genotype in the development of psychopathology in maltreated children. In Widom, C. S. (Ed.), Trauma, psychopathology, and violence: Causes, consequences, or correlates? (pp. 4975). New York: Oxford University Press.Google 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, 10471058.CrossRefGoogle Scholar
Jaffee, S. R., Caspi, A., Moffitt, T. E., & Taylor, A. (2004). Physical maltreatment victim to antisocial child: Evidence of an environmentally mediated process. Journal of Abnormal Psychology, 113, 4455.Google Scholar
Jirtle, R. L., & Skinner, M. K. (2007). Environmental epigenomics and disease susceptibility. Nature Reviews Genetics, 8, 253262.Google Scholar
Keers, R., & Aitchison, K. J. (2011). Pharmacogenetics of antidepressant response. Expert Review of Neurotherapeutics, 11, 101125.Google Scholar
Kendler, K. S. (2012). A conceptual overview of gene–environment interaction and correlation in a developmental context. In Kendler, K. S., Jaffee, S. R., & Romer, D. (Eds.), The dynamic genome and mental health: The role of genes and environments in youth development (pp. 528). New York: Oxford University Press.Google Scholar
Kendler, K. S., & Baker, J. H. (2007). Genetic influences on measures of the environment: A systematic review. Psychological Medicine, 37, 615626.Google Scholar
Kendler, K. S., & Eaves, L. J. (1986). Models for the joint effect of genotype and environment on liability to psychiatric illness. American Journal of Psychiatry, 143, 279289.Google ScholarPubMed
Kendler, K. S., & Gardner, C. O. (2010). Dependent stressful life events and prior depressive episodes in the prediction of major depression. Archives of General Psychiatry, 67, 11201127.Google Scholar
Kendler, K. S., Gardner, C., & Dick, D. M. (2011). Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction. Psychological Medicine, 41, 15071516.Google Scholar
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, 903913.Google Scholar
Klein, A. B., Williamson, R., Santini, M. A., Clemmensen, C., Ettrup, A., Rios, M., et al. (2011). Blood BDNF concentrations reflect brain-tissue BDNF levels across species. International Journal of Neuropsychopharmacology, 14, 347353.Google Scholar
Knopik, V. S., Heath, A. C., Jacob, T., Slutske, W. S., Bucholz, K. K., Madden, P. A. F., et al. (2006). Maternal alcohol use disorder and offspring ADHD: Disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine, 36, 14611471.Google Scholar
Kuntsi, J., Rijsdijk, F., Ronald, A., Asherson, P., & Plomin, R. (2005). Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood. Biological Psychiatry, 57, 647654.Google Scholar
Kuratomi, G., Iwamoto, K., Bundo, M., Kusumi, I., Kato, N., Iwata, N., et al. (2008). Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Molecular Psychiatry, 13, 429441.Google Scholar
Labonte, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., et al. (2012a). Genome-wide epigenetic regulation by early-life trauma. Archives of General Psychiatry, 69, 722731.Google Scholar
Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., et al. (2012b). Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry, 72, 4148.Google Scholar
Lander, E. S. (1996). The new genomics: Global views of biology. Science, 274, 536539.Google Scholar
Larsson, H., Dilshad, R., Lichtenstein, P., & Barker, E. D. (2011). Developmental trajectories of DSM-IV symptoms of attention-deficit/hyperactivity disorder: Genetic effects, family risk and associated psychopathology. Journal of Child Psychology and Psychiatry, 52, 954963.Google Scholar
Latendresse, S. J., Bates, J. E., Goodnight, J. A., Lansford, J. E., Budde, J. P., Goate, A., et al. (2011). Differential susceptibility to adolescent externalizing trajectories: Examining the interplay between CHRM2 and peer group antisocial behavior. Child Development, 82, 17971814.Google Scholar
Lee, M. P. (2012). Allele-specific gene expression and epigenetic modifications and their application to understanding inheritance and cancer. Biochimica et Biophysica Acta, 1819, 739742.Google Scholar
Lee, S. H., Wray, N. R., Goddard, M. E., & Visscher, P. M. (2011). Estimating missing heritability for disease from genome-wide association studies. American Journal of Human Genetics, 88, 294305.Google Scholar
Le-Niculescu, H., Kurian, S. M., Yehyawi, N., Dike, C., Patel, S. D., Edenberg, H. J., et al. (2009). Identifying blood biomarkers for mood disorders using convergent functional genomics. Molecular Psychiatry, 14, 1143.Google Scholar
Leslie, A. M., & Thaiss, L. (1992). Domain specificity in conceptual development: Neuropsychological evidence from autism. Cognition, 43, 225251.Google Scholar
Leve, L. D., Neiderhiser, J. M., Ge, X., Scaramella, L. V., Conger, R. D., Reid, J. B., et al. (2007). The early growth and development study: A prospective adoption design. Twin Research and Human Genetics, 10, 8495.Google Scholar
Levy, D., Ronennus, M., Yamrom, B., Lee, Y. H., Leotta, A., Kendall, J., et al. (2011). Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron, 70, 886897.Google Scholar
Lewi, L., Debrest, J., Dennes, W. J. B., & Fisk, N. M. (2006). Twin-to-twin transfusion syndrome. In van Vugt, J. M. G. & Shulman, L. P. (Eds.), Prenatal medicine (pp. 447472). New York: Taylor & Francis.Google Scholar
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., et al. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science, 277, 1662.CrossRefGoogle ScholarPubMed
Lubke, G. H., Hottenga, J. J., Walters, R., Laurin, C., de Geus, E. J. C., Willemsen, G., et al. (2012). Estimating the genetic variance of major depressive disorder due to all single nucleotide polymorphisms. Biological Psychiatry, 72, 707709.Google Scholar
Lundstrom, S., Chang, Z., Rastam, M., Gillberg, C., Larsson, H., Anckarsater, H., et al. (2012). Autism spectrum disorders and autistic-like traits: Similar etiology in the extreme end and the normal variation. Archives of General Psychiatry, 69, 4652.Google Scholar
Lynam, D. R., Caspi, A., Moffitt, T. E., Wikstrom, P. O. H., Loeber, R., & Novak, S. (2000). The interaction between impulsivity and neighborhood context on offending: The effects of impulsivity are stronger in poorer neighborhoods. Journal of Abnormal Psychology, 109, 563574.Google Scholar
Machin, G. A., & Keith, L. G. (1999). An atlas of multiple pregnancy: Biology and pathology. Pearl River, NY: Parthenon.Google Scholar
Malhotra, A. K., Zhang, J. P., & Lencz, T. (2012). Pharmacogenetics in psychiatry: Translating research into clinical practice. Molecular Psychiatry, 17, 760769.Google Scholar
Malhotra, D., McCarthy, S., Michaelson, J. J., Vacic, V., Burdick, K. E., Yoon, S., et al. (2011). High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron, 72, 951963.Google Scholar
Malhotra, D., & Sebat, J. (2012). CNVs: Harbingers of a rare variant revolution in psychiatric genetics. Cell, 148, 12231241.Google Scholar
Mannik, J., Vaas, P., Rull, K., Teesalu, P., Rebane, T., & Laan, M. (2010). Differential expression profile of growth hormone/chorionic somatomammotropin genes in placenta of small- and large-for-gestational-age newborns. Journal of Clinical Endocrinology & Metabolism, 95, 24332442.Google Scholar
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., et al. (2009). Finding the missing heritability of complex diseases. Nature, 461, 747753.Google Scholar
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342348.Google Scholar
McGue, M., Keyes, M., Sharma, A., Elkins, I., Legrand, L., Johnson, W., et al. (2007). The environments of adopted and non-adopted youth: Evidence on range restriction from the Sibling Interaction and Behavior Study. Behavior Genetics, 37, 449462.Google Scholar
McMahon, F. J., & Insel, T. R. (2012). Pharmacogenomics and personalized medicine in neuropsychiatry. Neuron, 74, 773776.Google Scholar
Meaburn, E. L., Schalkwyk, L. C., & Mill, J. (2010). Allele-specific methylation in the human genome: Implications for genetic studies of complex disease. Epigenetics, 5, 578582.Google Scholar
Mericq, V., Medina, P., Kakarieka, E., Marquez, L., Johnson, M., & Iniguez, G. (2009). Differences in expression and activity of 11 beta-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender. European Journal of Endocrinology, 161, 419425.Google Scholar
Meyer, J. M., Rutter, M., Silberg, J. L., Maes, H. H., Simonoff, E., Shillady, L. L., et al. (2000). Familial aggregation for conduct disorder symptomatology: The role of genes, marital discord and family adaptability. Psychological Medicine, 30, 759774.Google Scholar
Meyer-Lindenberg, A. (2012). The future of fMRI and genetics research. NeuroImage, 62, 12861292.Google Scholar
Meyer-Lindenberg, A., Buckholtz, J. W., Kolachana, B., Hariri, A. R., Pezawas, L., Blasi, G., et al. (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences, 103, 62696274.Google Scholar
Mill, J. (2012). Epigenetic effects on gene function and their role in mediating gene–environment interactions. In Kendler, K. S., Jaffee, S. R., & Romer, D. (Eds.), The dynamic genome and mental health: The role of genes and environments in youth development (pp. 145171). New York: Oxford University Press.Google Scholar
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., et al. (2009). Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proceedings of the National Academy of Sciences, 106, 1471614721.Google Scholar
Miller, G. E., Chen, E., & Parker, K. J. (2011). Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms. Psychological Bulletin, 137, 959997.Google Scholar
Moffitt, T. E., Caspi, A., & Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62, 473481.Google Scholar
Morozov, A. (2008). Conditional gene expression and targeting in neuroscience research. Current Protocols in Neuroscience, 44, 4.31.1–4.31.10.Google Scholar
Mueller, B. R., & Bale, T. L. (2008). Sex-specific programming of offspring emotionality after stress early in pregnancy. Journal of Neuroscience, 28, 90559065.Google Scholar
Mulle, J. G. (2012). Schizophrenia genetics: Progress, at last. Current Opinion in Genetics and Development, 22, 238244.Google Scholar
Müller, U. (1999). Ten years of gene targeting: Targeted mouse mutants, from vector design to phenotype analysis. Mechanisms of Development, 82, 321.Google Scholar
Munafo, M. R., Brown, S. M., & Hariri, A. R. (2008). Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry, 63, 852857.Google Scholar
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmuhl, Y., Fischer, D., et al. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12, 1559–U108.Google Scholar
Neiderhiser, J. M., Leve, L. D., Ge, X., Scaramella, L. V., Conger, R. D., Reid, J. B., et al. (2007). The impact of prenatal drug exposure on toddler behavior: Distinguishing genetic effects from exposure using an adoption design. Behavior Genetics, 37, 780.Google Scholar
Newman, T. K., Syagailo, Y. V., Barr, C. S., Wendland, J. R., Champoux, M., Graessle, M., et al. (2005). Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys. Biological Psychiatry, 57, 167172.Google Scholar
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97106.Google Scholar
Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., et al. (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature, 411, 603606.Google Scholar
Ouellet-Morin, I., Danese, A., Bowes, L., Shakoor, S., Ambler, A., Pariante, C. M., et al. (2011). A discordant monozygotic twin design shows blunted cortisol reactivity among bullied children. Journal of the American Academy of Child & Adolescent Psychiatry, 50, 574582.Google Scholar
Passamonti, L., Fera, F., Magariello, A., Cerasa, A., Gioia, M. C., Muglia, M., et al. (2006). Monoamine oxidase A genetic variations influence brain activity associated with inhibitory control: New insight into the neural correlates of impulsivity. Biological Psychiatry, 59, 334340.Google Scholar
Patterson, G. R., DeBaryshe, B. D., & Ramsey, E. (1989). A developmental perspective on antisocial behavior. American Psychologist, 44, 329335.Google Scholar
Pennisi, E. (2003). Human genome—A low number wins the GeneSweep pool. Science, 300, 1484.Google Scholar
Pine, D. S., Ernst, M., & Leibenluft, E. (2010). Imaging genetics applications in child psychiatry. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 772782.Google Scholar
Plomin, R., & Kovas, Y. (2005). Generalist genes and learning disabilities. Psychological Bulletin, 131, 592617.Google Scholar
Plomin, R., & Daniels, D. (1987). Why are children in the same family so different from one another? Behavioral & Brain Sciences, 10, 116.Google Scholar
Plomin, R., DeFries, J. C., & Loehlin, J. C. (1977). Genotype–environment interaction and correlation in the analysis of human behavior. Psychological Bulletin, 84, 309322.Google Scholar
Plomin, R., DeFries, J. C., McClearn, G. E., & McGuffin, P. (2008). Behavioral genetics. (5 ed.) New York: Worth Publishers.Google Scholar
Price, T. S., Simonoff, E., Asherson, P., Curran, S., Kuntsi, J., Waldman, I., et al. (2005). Continuity and change in preschool ADHD symptoms: Longitudinal genetic analysis with contrast effects. Behavior Genetics, 35, 121132.Google Scholar
Pritchard, J. K., & Cox, N. J. (2002). The allelic architecture of human disease genes: Common disease—Common variant . . . or not? Human Molecular Genetics, 11, 24172423.Google Scholar
Raison, C. L., Lowry, C. A., & Rook, G. A. (2010). Inflammation, sanitation, and consternation: Loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression. Archives of General Psychiatry, 67, 12111224.Google Scholar
Reiss, D., Neiderhiser, J. M., Hetherington, E. M., & Plomin, R. (2000). The relationship code: Deciphering genetic and social influences on adolescent development. Cambridge, MA: Harvard University Press.Google Scholar
Relton, C. L., & Smith, G. D. (2012). Is epidemiology ready for epigenetics? International Journal of Epidemiology, 41, 59.Google Scholar
Rietveld, M. J. H., Hudziak, J. J., Bartels, M., van Beijsterveldt, C. E. M., & Boomsma, D. I. (2004). Heritability of attention problems in children: Longitudinal results from a study of twins, age 3 to 12. Journal of Child Psychology and Psychiatry, 45, 577588.Google Scholar
Rijsdijk, F. V., & Sham, P. (2002). Analytic approaches to twin data using structural equation models. Briefings in Bioinformatics, 3, 119133.Google Scholar
Roberts, A. D., Moor, C. F., DeJesus, O. T., Barnhart, T. E., Larson, J. A., Mukherjee, J., et al. (2004). Prenatal stress, moderate fetal alcohol, and dopamine system function in rhesus monkeys. Neurotoxicology and Teratology, 26, 169178.Google Scholar
Robinson, E. B., Koenen, K. C., McCormick, M. C., Munir, K., Hallett, V., Happe, F., et al. (2011). Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). Archives of General Psychiatry, 68, 11131121.Google Scholar
Rollins, B., Martin, M. V., Morgan, L., & Vawter, M. P. (2010). Analysis of whole genome biomarker expression in blood and brain. American Journal of Medical Genetics, 153B, 919936.Google Scholar
Ronald, A. (2011). Is the child “father of the man”? Evaluating the stability of genetic influences across development. Developmental Science, 14, 14711478.Google Scholar
Ronald, A., Happe, F., Price, T. S., Baron-Cohen, S., & Plomin, R. (2006). Phenotypic and genetic overlap between autistic traits at the extremes of the general population. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 12061214.Google Scholar
Rosa, A., Picchioni, M. M., Kalidindi, S., Loat, C. S., Knight, J., Toulopoulou, T., et al. (2008). Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins. American Journal of Medical Genetics, 147B, 459462.Google Scholar
Roth, T. L., & Sweatt, J. (2011). Epigenetic mechanisms and environmental shaping of the brain during sensitive periods of development. Journal of Child Psychology and Psychiatry, 52, 398408.Google Scholar
Rothman, K. J., Greenland, S., & Lash, T. L. (2008). Modern epidemiology (3rd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
Rucker, J. J. H., & McGuffin, P. (2012). Genomic structural variation in psychiatric disorders. Development and Psychopathology, 24, 13351344.Google Scholar
Rutter, M., & Silberg, J. (2002). Gene–environment interplay in relation to emotional and behavioral disturbance. Annual Review of Psychology, 53, 463490.Google Scholar
Sabol, S., Hu, S., & Hamer, D. (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics, 103, 273279.Google Scholar
Schneider, M. L., Moore, C. F., & Adkins, M. M. (2011). The effects of prenatal alcohol exposure on behavior: Rodent and primate studies. Neuropsychology Review, 21, 186203.Google Scholar
Shonkoff, J. P., Garner, A. S., Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, Section on Developmental and Behavioral Pediatrics, et al. (2012). The lifelong effects of childhood adversity and toxic stress. Pediatrics, 129, e232e246.Google Scholar
Shulman, L. P., & Cohen, L. (2006). Prenatal diagnosis of multifetal pregnancies. In van Vugt, J. M. G. & Shulman, L. P. (Eds.), Prenatal medicine (pp. 205218). New York: Taylor & Francis Group.Google Scholar
Shumay, E., Logan, J., Volkow, N. D., & Fowler, J. S. (2012). Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAOA enzyme in healthy men. Epigenetics, 7, 11511160.Google Scholar
Simmons, J. P., Nelson, L. D., & Simonsohn, U. (2011). False-positive psychology: Undisclosed flexibility in data collection and analysis allows presenting anything as significant. Psychological Science, 22, 13591366.Google Scholar
Sroufe, L. A., & Rutter, M. (1984). The domain of developmental psychopathology. Child Development, 55, 1729.Google Scholar
Stankiewicz, P., & Lupski, J. R. (2010). Structural variation in the human genome and its role in disease. Annual Review of Medicine, 437455.CrossRefGoogle ScholarPubMed
State, M., & Levitt, P. (2011). The conundrums of understanding genetic risks for autism spectrum disorders. Nature Neuroscience, 14, 14991506.Google Scholar
Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O. P. H., Ingason, A., Steinberg, S., et al. (2008). Large recurrent microdeletions associated with schizophrenia. Nature, 455, 232–U61.Google Scholar
Stoolmiller, M. (1999). Implications of the restricted range of family environments for estimates of heritability and nonshared environment in behavior–genetic adoption studies. Psychological Bulletin, 125, 392409.Google Scholar
Sullivan, E. L., Grayson, B., Takahashi, D., Robertson, N., Maier, A., Bethea, C. L., et al. (2010). Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. Journal of Neuroscience, 30, 38263830.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, 983988.Google Scholar
Talmud, P. J., Hingorani, A. D., Cooper, J. A., Marmot, M. G., Brunner, E. J., Kumari, M., et al. (2010). Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. British Medical Journal, 340(7739), 192.Google Scholar
Taylor, M. J., Sen, S., & Bhagwagar, Z. (2010). Antidepressant response and the serotonin transporter gene-linked polymorphic region. Biological Psychiatry, 68, 536543.Google Scholar
Timberlake, D. S., Hopfer, C. J., Rhee, S. H., Friedman, N. P., Haberstick, B. C., Lessem, J. M., et al. (2007). College attendance and its effect on drinking behaviors in a longitudinal study of adolescents. Alcoholism: Clinical & Experimental Research, 31, 10201030.Google Scholar
Timberlake, D. S., Rhee, S. H., Haberstick, B. C., Hopfer, C., Ehringer, M., Lessem, J. M., et al. (2006). The moderating effects of religiosity on the genetic and environmental determinants of smoking initiation. Nicotine & Tobacco Research, 8, 123133.Google Scholar
Torres, K. C. L., Souza, B. R., Miranda, D. M., Nicolato, R., Neves, F. S., Barros, A. G. A., et al. (2009). The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 33, 214219.Google Scholar
Tung, J., Akinyi, M. Y., Mutura, S., Altmann, J., Wray, G. A., & Alberts, S. C. (2011). Allele-specific gene expression in a wild nonhuman primate population. Molecular Ecology, 20, 725739.Google Scholar
Tung, J., Barreiro, L. B., Johnson, Z. P., Hansen, K. D., Michopoulos, V., Toufexis, D., et al. (2012). Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proceedings of the National Academy of Sciences, 109, 64906495.Google Scholar
Turkheimer, E. (2000). Three laws of behavior genetics and what they mean. Current Directions in Psychological Science, 9, 160164.Google Scholar
Turkheimer, E., & Waldron, M. (2000). Non-shared environment: A theoretical, methodological, and quantitative review. Psychological Bulletin, 126, 78108.Google Scholar
Uher, R., & McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15, 1822.Google Scholar
Uher, R., Perroud, N., Ng, M. Y. M., Hauser, J., Henigsberg, N., Maier, W., et al. (2010). Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. American Journal of Psychiatry, 167, 555564.Google Scholar
Uher, R., Caspi, A., Houts, R., Sugden, K., Williams, B., Poulton, R., et al. (2011). Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: Replications and implications for resolving inconsistent results. Journal of Affective Disorders, 135, 5665.Google Scholar
van Dongen, J., Slagboom, P., Draisma, H. H., Martin, N. G., & Boomsma, D. I. (2012). The continuing value of twin studies in the omics era. Nature Reviews Genetics, 13, 640653.Google Scholar
Veenma, D., Brosens, E., de Jong, E., van de Ven, C., Meeussen, C., Cohen-Overbeek, T., et al. (2012). Copy number detection in discordant monozygotic twins of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) cohorts. European Journal of Human Genetics, 20, 298304.Google Scholar
Veltman, J. A., & Brunner, H. G. (2012). De novo mutations in human genetic disease. Nature Reviews Genetics, 13, 565575.Google Scholar
Victoria, A., Mora, G., & Arias, F. (2001). Perinatal outcome, placental pathology, and severity of discordance in monochorionic and dichorionic twins. Obstetrics and Gynecology, 97, 310315.Google Scholar
Viding, E., Jones, A. P., Frick, P. J., Moffitt, T. E., & Plomin, R. (2008). Heritability of antisocial behaviour at 9: Do callous–unemotional traits matter? Developmental Science, 11, 1722.Google Scholar
Vinkhuyzen, A. A. E., Pedersen, N. L., Yang, J., Lee, S. H., Magnusson, P. K. E., Iacono, W. G., et al. (2012). Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion. Translational Psychiatry, 2, e102.Google Scholar
Visscher, P. M., Medland, S. E., Ferreira, M. A. R., Morley, K. I., Zhu, G., Cornes, B. K., et al. (2006). Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings. PLoS Genetics, 2, 316325.Google Scholar
Vissers, L. E., de Ligt, J., Gilissen, C., Janssen, I., Steehouwer, M., de Vries, P., et al. (2010). A de novo paradigm for mental retardation. Nature Genetics, 42, 11091112.Google Scholar
Vitaro, F., Brendgen, M., & Arsenault, L. (2009). The discordant MZ-twin method: One step closer to the holy grail of causality. International Journal of Behavioral Development, 33, 376382.Google Scholar
Vlietinck, R., Derom, R., Neale, M. C., Maes, H., Vanloon, H., Derom, C., et al. (1989). Genetic and environmental variation in the birth-weight of twins. Behavior Genetics, 19, 151161.Google Scholar
Vucetic, Z., Kimmel, J., Totoki, K., Hollenbeck, E., & Reyes, T. M. (2010). Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology, 151, 47564764.Google Scholar
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847854.Google Scholar
Weaver, I. C. G., Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., et al. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. Journal of Neuroscience, 25, 1104511054.Google Scholar
Weaver, I. C. G., Meaney, M. J., & Szyf, M. (2006). Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proceedings of the National Academy of Sciences, 103, 34803485.Google Scholar
Wellman, H. M., Cross, D., & Watson, J. (2001). Meta-analysis of theory-of-mind development: The truth about false belief. Child Development, 72, 655684.Google Scholar
Willeit, M., & Praschak-Rieder, N. (2010). Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry. NeuroImage, 53, 878892.Google Scholar
Williams, H. J., Moskvina, V., Smith, R. L., Dwyer, S., Russo, G., Owen, M. J., et al. (2011). Association between TCF4 and schizophrenia does not exert its effect by common nonsynonymous variation or by influencing cis-acting regulation of mRNA expression in adult human brain. American Journal of Medical Genetics, 156B, 781784.Google Scholar
Williams-Gray, C. H., Hampshire, A., Barker, R. A., & Owen, A. M. (2008). Attentional control in Parkinson's disease is dependent on COMT val(158)met genotype. Brain, 131, 397408.Google Scholar
Wise, R. A. (2004). Dopamine, learning and motivation. Nature Reviews Neuroscience, 5, 483494.Google Scholar
Wray, N. R., Goddard, M. E., & Visscher, P. M. (2007). Prediction of individual genetic risk to disease from genome-wide association studies. Genome Research, 17, 15201528.Google Scholar
Wray, N. R., Purcell, S. M., & Visscher, P. M. (2011). Synthetic associations created by rare variants do not explain most GWAS results. PLoS Biology, 9(1), e1000579.Google Scholar
Wright, S. (1921). Systems of mating. II. The effects of inbreeding on the genetic composition of a population. Genetics, 6, 124143.Google Scholar
Wu, K., O'Keeffe, D., Politis, M., O'Keeffe, G. C., Robbins, T. W., Bose, S. K., et al. (2012). The catechol-O-methyltransferase Val(158)Met polymorphism modulates fronto-cortical dopamine turnover in early Parkinson's disease: A PET study. Brain, 135, 24492457.Google Scholar
Xu, B., Ionita-Laza, I., Roose, S. P., Boone, B., Woodrick, S., Sun, Y., et al. (2012). De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nature Genetics, 44, 13651369.Google Scholar
Yang, J. A., Benyamin, B., Mcevoy, B. P., Gordon, S., Henders, A. K., Nyholt, D. R., et al. (2010). Common SNPs explain a large proportion of the heritability for human height. Nature Genetics, 42, 565–U131.Google Scholar
Zhang, T. Y., & Meaney, M. J. (2010). Epigenetics and the environmental regulation of the genome and its function. Annual Review of Psychology, 61, 439466.Google Scholar