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Using genetic designs to identify likely causal environmental contributions to psychopathology

Published online by Cambridge University Press:  06 October 2022

Ruth Sellers ,
Lucy Riglin ,
Gordon T. Harold  and
Anita Thapar Open the ORCID record for Anita Thapar [Opens in a new window]
Ruth Sellers*
Affiliation:
Brighton & Sussex Medical School, University of Sussex, Brighton, UK
Lucy Riglin
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK Wolfson Centre for Young People’s Mental Health, Cardiff University, Cardiff, UK
Gordon T. Harold
Affiliation:
Faculty of Education, University of Cambridge, Cambridge, UK School of Medicine, Child and Adolescent Psychiatry Unit, University College Dublin, Dublin, Ireland
Anita Thapar
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK Wolfson Centre for Young People’s Mental Health, Cardiff University, Cardiff, UK
*
Corresponding author: Ruth Sellers, email: r.sellers@sussex.ac.uk
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Abstract

The multifactorial nature of psychopathology, whereby both genetic and environmental factors contribute risk, has long been established. In this paper, we provide an update on genetically informative designs that are utilized to disentangle genetic and environmental contributions to psychopathology. We provide a brief reminder of quantitative behavioral genetic research designs that have been used to identify potentially causal environmental processes, accounting for genetic contributions. We also provide an overview of recent molecular genetic approaches that utilize genome-wide association study data which are increasingly being applied to questions relevant to psychopathology research. While genetically informative designs typically have been applied to investigate the origins of psychopathology, we highlight how these approaches can also be used to elucidate potential causal environmental processes that contribute to developmental course and outcomes. We highlight the need to use genetically sensitive designs that align with intervention and prevention science efforts, by considering strengths-based environments to investigate how positive environments can mitigate risk and promote children’s strengths.

Keywords

environmentgeneticspsychopathologystrength-based approaches
Type
Special Issue Article
Information
Development and Psychopathology , Volume 34 , Issue 5: Special Section: Leveraging Genetically Informative Study Designs to Understand the Development and Familial Transmission of Psychopathology , December 2022 , pp. 1653 - 1665
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Arseneault, L., Milne, B. J., Taylor, A., Adams, F., Delgado, K., Caspi, A., & Moffitt, T. E. (2008). Being bullied as an environmentally mediated contributing factor to children’s internalizing problems: A study of twins discordant for victimization. Archives of Pediatrics and Adolescent Medicine, 162(2), 145–150. https://doi.org/10.1001/archpediatrics.2007.53 CrossRefGoogle ScholarPubMed
Aschard, H., Lutz, S., Maus, B., Duell, E. J., Fingerlin, T. E., Chatterjee, N., Kraft, P, & Van Steen, K. (2012). Challenges and opportunities in genome-wide environmental interaction (GWEI) studies. Human Genetics, 131(10), 1591–1613. https://doi.org/10.1007/s00439-012-1192-0CrossRefGoogle ScholarPubMed
Assary, E., Vincent, J. P., Keers, R., & Pluess, M. (2018, May). Gene-environment interaction and psychiatric disorders: Review and future directions. In Seminars in cell & developmental biology (Vol. 77, pp. 133–143). Academic Press. https://doi.org/10.1016/j.semcdb.2017.10.016 Google Scholar
Ben-Naim, S., Gill, N., Laslo-Roth, R., & Einav, M. (2019). Parental stress and parental self-efficacy as mediators of the association between children’s ADHD and marital satisfaction. Journal of attention disorders, 23(5), 506–516.CrossRefGoogle ScholarPubMed
Bogdan, R., Baranger, D. A., & Agrawal, A. (2018). Polygenic risk scores in clinical psychology: Bridging genomic risk to individual differences. Annual Review of Clinical Psychology, 14, 119–157. https://doi.org/10.1146/annurev-clinpsy-050817-084847 CrossRefGoogle ScholarPubMed
Broderick, A. V., & Neiderhiser, J. M. (2019). Genetics and parenting. In Bornstein, M. H. (Ed.), Handbook of parenting: Biology and ecology of parenting (pp. 123–165). Routledge/Taylor & Francis Group. https://doi.org/10.4324/9780429401459-4 CrossRefGoogle Scholar
Brumpton, B., Sanderson, E., Heilbron, K., Hartwig, F. P., Harrison, S., Vie, G.Å., Cho, Y., Howe, L. D., Hughes, A, Boomsma, D. I., & Havdahl, A. (2020). Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Nature Communications, 11(1), 3519. https://doi.org/10.1038/s41467-020-17117-4 CrossRefGoogle ScholarPubMed
Burt, S. A. (2009). Rethinking environmental contributions to child and adolescent psychopathology: A meta-analysis of shared environmental influences. Psychological Bulletin, 135(4), 608–637. https://doi.org/10.1037/a0015702 CrossRefGoogle ScholarPubMed
Caspi, A., Moffitt, T. E., Morgan, J., Rutter, M., Taylor, A., Arseneault, L., Tully, L., Jacobs, C., Kim-Cohen, J., & Polo-Tomas, M. (2004). Maternal expressed emotion predicts children’s antisocial behavior problems: Using monozygotic-twin differences to identify environmental effects on behavioral development. Developmental Psychology, 40(2), 149–161. https://doi.org/10.1037/0012-1649.40.2.149 CrossRefGoogle ScholarPubMed
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8(4), 597–600. https://doi.org/10.1017/S0954579400007318 CrossRefGoogle Scholar
Colodro-Conde, L., Couvy-Duchesne, B., Whitfield, J. B., Streit, F., Gordon, S., Kemper, K. E., Yengo, L., Zheng, Z., Trzaskowski, M., De Zeeuw, E. L., & Nivard, M. G. (2018). Association between population density and genetic risk for schizophrenia. JAMA Psychiatry, 75(9), 901–910. https://doi.org/10.1001/jamapsychiatry.2018.1581 CrossRefGoogle ScholarPubMed
D’Onofrio, B. M., Slutske, W. S., Turkheimer, E., Emery, R. E., Harden, K. P., Heath, A. C., Madden, P. A., & Martin, N. G. (2007). Intergenerational transmission of childhood conduct problems: A children of twins study. Archives of General Psychiatry, 64(7), 820–829. https://doi.org/10.1001/archpsyc.64.7.820 CrossRefGoogle ScholarPubMed
Dass, S. A. H., McCracken, K., Pokhvisneva, I., Chen, L. M., Garg, E., Nguyen, T. T., Wang, Z., Barth, B., Yaqubi, M., McEwen, L. M., & MacIsaac, J. L. (2019). A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions. EBioMedicine, 42, 188–202. https://doi.org/10.1101/289983 CrossRefGoogle Scholar
Davey Smith, G. D., Richmond, R., & Pingault, J.-B. (2022). Combining human genetics and causal inference to understand human disease and development. Cold Spring Harbor Laboratory Press.Google Scholar
de Zeeuw, E. L., Hottenga, J.-J., Ouwens, K. G., Dolan, C. V., Ehli, E. A., Davies, G. E., Boomsma, D. I., & van Bergen, E. (2020). Intergenerational transmission of education and ADHD: Effects of parental genotypes. Behavior Genetics, 50(4), 221–232. https://doi.org/10.1007/s10519-020-09992-w CrossRefGoogle ScholarPubMed
Deater-Deckard, K., Ivy, L., & Petrill, S. A. (2006). Maternal warmth moderates the link between physical punishment and child externalizing problems: A parent-offspring behavior genetic analysis. Parenting: Science and Practice, 6(1), 59–78. https://doi.org/10.1207/s15327922par0601_3 CrossRefGoogle Scholar
Dvorsky, M. R., & Langberg, J. M. (2016). A review of factors that promote resilience in youth with ADHD and ADHD symptoms. Clinical Child and Family Psychology Review, 19(4), 368–391. https://doi.org/10.1007/s10567-016-0216-z CrossRefGoogle ScholarPubMed
Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 24(4), 562–575. https://doi.org/10.1038/s41380-018-0070-0 CrossRefGoogle ScholarPubMed
Ganiban, J. M., Liu, C., Zappaterra, L., An, S., Natsuaki, M. N., Neiderhiser, J. M., Reiss, D., Shaw, D. S., & Leve, L. D. (2021). Gene× environment interactions in the development of preschool effortful control, and its implications for childhood externalizing behavior. Behavior Genetics, 51(5), 448–462. https://doi.org/10.1007/s10519-021-10073-9 CrossRefGoogle ScholarPubMed
Ge, X., Conger, R. D., Cadoret, R. J., Neiderhiser, J. M., Yates, W., Troughton, E., & Stewart, M. A. (1996). The developmental interface between nature and nurture: A mutual influence model of child antisocial behavior and parent behaviors. Developmental Psychology, 32(4), 574–589.CrossRefGoogle Scholar
Grotzinger, A. D., Rhemtulla, M., de Vlaming, R., Ritchie, S. J., Mallard, T. T., Hill, W. D., Ip, H. F., Marioni, R. E., McIntosh, A. M., Deary, I. J., & Koellinger, P. D. (2019). Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nature Human Behaviour, 3(5), 513–525. https://doi.org/10.1038/s41562-019-0566-x CrossRefGoogle ScholarPubMed
Gustavson, K., Ystrom, E., Stoltenberg, C., Susser, E., Surén, P., Magnus, P., Knudsen, G. P., Smith, G. D., Langley, K., Rutter, M., & Aase, H. (2017). Smoking in pregnancy and child ADHD. Pediatrics, 139(2), e20162509.CrossRefGoogle ScholarPubMed
Harold, G. T., Elam, K. K., Lewis, G., Rice, F., & Thapar, A. (2012). Interparental conflict, parent psychopathology, hostile parenting, and child antisocial behavior: Examining the role of maternal versus paternal influences using a novel genetically sensitive research design. Development and Psychopathology, 24(4), 1283–1295. https://doi.org/10.1017/S0954579412000703 CrossRefGoogle ScholarPubMed
Harold, G. T., Leve, L. D., Barrett, D., Elam, K., Neiderhiser, J. M., Natsuaki, M. N., Shaw, D. S., Reiss, D., & Thapar, A. (2013). Biological and rearing mother influences on child ADHD symptoms: Revisiting the developmental interface between nature and nurture. Journal of Child Psychology and Psychiatry and Allied Disciplines, 54(10), 1038–1046. https://doi.org/10.1111/jcpp.12100 CrossRefGoogle ScholarPubMed
Harold, G. T., Leve, L. D., & Sellers, R. (2017). How can genetically informed research help inform the next generation of interparental and parenting interventions? Child Development, 88(2), 446–458. https://doi.org/10.1111/cdev.12742 CrossRefGoogle ScholarPubMed
Harold, G. T., & Sellers, R. (2018). Annual research review: Interparental conflict and youth psychopathology: An evidence review and practice focused update. Journal of Child Psychology and Psychiatry, 59(4), 374–402. https://doi.org/10.1111/jcpp.12893 CrossRefGoogle ScholarPubMed
Hemani, G., Bowden, J., & Davey Smith, G. (2018). Evaluating the potential role of pleiotropy in Mendelian randomization studies. Human Molecular Genetics, 27(R2), R195–R208. https://doi.org/10.1093/hmg/ddy163 CrossRefGoogle ScholarPubMed
Henry, J., Dionne, G., Viding, E., Vitaro, F., Brendgen, M., Tremblay, R. E., & Boivin, M. (2018). Early warm-rewarding parenting moderates the genetic contributions to callous-unemotional traits in childhood. Journal of Child Psychology and Psychiatry, 59(12), 1282–1288. https://doi.org/10.1111/jcpp.12918 CrossRefGoogle ScholarPubMed
Horwitz, B. N., Reynolds, C. A., Walum, H., Ganiban, J., Spotts, E. L., Reiss, D., Lichtenstein, P., & Neiderhiser, J. M. (2016). Understanding the role of mate selection processes in couples’ pair-bonding behavior. Behavior Genetics, 46(1), 143–149. https://doi.org/10.1007/s10519-015-9766-y CrossRefGoogle ScholarPubMed
Huang, A. Y., Yu, D., Davis, L. K., Sul, J. H., Tsetsos, F., Ramensky, V., Zelaya, I., Ramos, E. M., Osiecki, L., Chen, J. A., McGrath, L. M., Illmann, C., Sandor, P., Barr, C. L., Grados, M., Singer, H. S., Nöthen, M. M., Hebebrand, J., King, R. A., Dion, Y., …Coppola, G. (2017). Rare copy number variants in NRXN1 and CNTN6 increase risk for tourette syndrome. Neuron, 94(6), 1101–1111.e7. https://doi.org/10.1016/j.neuron.2017.06.010 CrossRefGoogle ScholarPubMed
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(6), 1047. https://doi.org/10.1037/0021-843X.113.1.44 CrossRefGoogle Scholar
Jaffee, S. R., Moffitt, T. E., Caspi, A., Fombonne, E., Poulton, R., & Martin, J. (2002). Differences in early childhood risk factors for juvenile-onset and adult-onset depression. Archives of General Psychiatry, 59(3), 215–222. https://doi.org/10.1001/archpsyc.59.3.215 CrossRefGoogle ScholarPubMed
Jaffee, S. R., & Price, T. S. (2008). Genotype-environment correlations: Implications for determining the relationship between environmental exposures and psychiatric illness. Psychiatry-interpersonal and Biological Processes, 7(12), 496–499. https://doi.org/10.1016/j.mppsy.2008.10.002 Google ScholarPubMed
Jaffee, S. R., & Price, T. S. (2012). The implications of genotype-environment correlation for establishing causal processes in psychopathology. Development and Psychopathology, 24(4), 1253–1264. https://doi.org/10.1017/S0954579412000685 CrossRefGoogle ScholarPubMed
Jami, E. S., Hammerschlag, A. R., Bartels, M., & Middeldorp, C. M. (2021). Parental characteristics and offspring mental health and related outcomes: A systematic review of genetically informative literature. Translational Psychiatry, 11(1), 1–38. https://doi.org/10.1038/s41398-021-01300-2 CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2020). The rearing environment and risk for major depression: A Swedish national high-risk home-reared and adopted-away co-sibling control study. American Journal of Psychiatry, 177(5), 447–453. https://doi.org/10.1176/appi.ajp.2019.19090911 CrossRefGoogle ScholarPubMed
Knafo, A., & Jaffee, S. R. (2013). Gene-environment correlation in developmental psychopathology. Development and Psychopathology, 25(1), 1–6. https://doi.org/10.1017/S0954579412000855 CrossRefGoogle ScholarPubMed
Knafo-Noam, A., Vertsberger, D., & Israel, S. (2018). Genetic and environmental contributions to children’s prosocial behavior: Brief review and new evidence from a reanalysis of experimental twin data. Current Opinion in Psychology, 20, 60–65. https://doi.org/10.1016/j.copsyc.2017.08.013 CrossRefGoogle ScholarPubMed
Knopik, V. S., Neiderhiser, J. M., DeFries, J. C., & Plomin, R. (2017). Behavioral genetics (7th ed.). Worth Publishers, Macmillan Learning.Google Scholar
Kong, A., Thorleifsson, G., Frigge, M. L., Vilhjalmsson, B. J., Young, A. I., Thorgeirsson, T. E., Benonisdottir, S., Oddsson, A., Halldorsson, B. V., Masson, G., Gudbjartsson, D. F., Helgason, A., Bjornsdottir, G., Thorsteinsdottir, U., & Stefansson, K. (2018). The nature of nurture: Effects of parental genotypes. Science, 359(6374), 424–428. https://doi.org/10.1126/science.aan6877 CrossRefGoogle ScholarPubMed
Kousgaard, S. J., Boldsen, S. K., Mohr-Jensen, C., & Lauritsen, M. B. (2018). The effect of having a child with ADHD or ASD on family separation. Social psychiatry and psychiatric epidemiology, 53(12), 1391–1399.CrossRefGoogle ScholarPubMed
Lee, P. H., Anttila, V., Won, H., Feng, Y.-C. A., Rosenthal, J., Zhu, Z., & Smoller, J. W. (2019). Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell, 179(7), 1469–1482.e11. https://doi.org/10.1016/j.cell.2019.11.020 CrossRefGoogle Scholar
Leppert, B., Havdahl, A., Riglin, L., Jones, H. J., Zheng, J., Smith, G. D., Tilling, K., Thapar, A., Reichborn-Kjennerud, T., & Stergiakouli, E. (2019). Association of maternal neurodevelopmental risk alleles with early-life exposures. JAMA Psychiatry, 76(8), 834–842. https://doi.org/10.1001/jamapsychiatry.2019.0774 CrossRefGoogle ScholarPubMed
Leve, L. D., Harold, G. T., Ge, X., Neiderhiser, J. M., & Patterson, G. (2010). Refining intervention targets in family-based research: Lessons from quantitative behavioral genetics. Perspectives on Psychological Science, 5(5), 516–526. https://doi.org/10.1177/1745691610383506 CrossRefGoogle ScholarPubMed
Leve, L. D., Harold, G. T., Ge, X., Neiderhiser, J. M., Shaw, D., Scaramella, L. V., & Reiss, D. (2009). Structured parenting of toddlers at high versus low genetic risk: Two pathways to child problems. Journal of the American Academy of Child & Adolescent Psychiatry, 48(11), 1102–1109. https://doi.org/10.1097/CHI.0b013e3181b8bfc0 CrossRefGoogle ScholarPubMed
Leve, L. D., Neiderhiser, J. M., Ganiban, J. M., Natsuaki, M. N., Shaw, D. S., & Reiss, D. (2019). The Early Growth and Development Study: A dual-family adoption study from birth through adolescence. Twin Research and Human Genetics, 22(6), 716–727. https://doi.org/10.1017/thg.2019.66 CrossRefGoogle ScholarPubMed
Liu, C., & Neiderhiser, J. M. (2017). Using genetically informed designs to understand the environment: The importance of family-based approaches. In Gene-environment transactions in developmental psychopathology (pp. 95–110). Springer. https://doi.org/10.1007/978-3-319-49227-8_5 CrossRefGoogle Scholar
Luthar, S. S., & Brown, P. J. (2007). Maximizing resilience through diverse levels of inquiry: Prevailing paradigms, possibilities, and priorities for the future. Development and Psychopathology, 19(3), 931–955. https://doi.org/10.1017/S0954579407000454 CrossRefGoogle ScholarPubMed
Martin, A. R., Daly, M. J., Robinson, E. B., Hyman, S. E., & Neale, B. M. (2019). Predicting polygenic risk of psychiatric disorders. Biological Psychiatry, 86(2), 97–109. https://doi.org/10.1016/j.biopsych.2018.12.015 CrossRefGoogle ScholarPubMed
Martin, J., Wray, M., Agha, S. S., Lewis, K. J., Anney, R. J., O’Donovan, M. C., Thapar, A., & Langley, K. (2022). Investigating direct and indirect genetic effects in attention deficit hyperactivity disorder (ADHD) using parent-offspring trios. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2022.06.008 Google ScholarPubMed
McAdams, T. A., Hannigan, L. J., Eilertsen, E. M., Gjerde, L. C., Ystrom, E., & Rijsdijk, F. V. (2018). Revisiting the children-of-twins design: Improving existing models for the exploration of intergenerational associations. Behavior Genetics, 48(5), 397–412. https://doi.org/10.1007/s10519-018-9912-4 CrossRefGoogle ScholarPubMed
McAdams, T. A., Neiderhiser, J. M., Rijsdijk, F. V., Narusyte, J., Lichtenstein, P., & Eley, T. C. (2014). Accounting for genetic and environmental confounds in associations between parent and child characteristics: A systematic review of children-of-twins studies. Psychological Bulletin, 140(4), 1138. https://doi.org/10.1037/a0036416 CrossRefGoogle ScholarPubMed
Murray, G. K., Lin, T., Austin, J., McGrath, J. J., Hickie, I. B., & Wray, N. R. (2021). Could polygenic risk scores be useful in psychiatry?: A review. JAMA Psychiatry, 78(2), 210–219. https://doi.org/10.1001/jamapsychiatry.2020.3042 CrossRefGoogle ScholarPubMed
Narusyte, J., Neiderhiser, J. M., DʼOnofrio, B. M., Reiss, D., Spotts, E. L., Ganiban, J., & Lichtenstein, P. (2008). Testing different types of genotype-environment correlation: An extended children-of-twins model. Developmental Psychology, 44(6), 1591. https://doi.org/10.1037/a0013911 CrossRefGoogle ScholarPubMed
Neiderhiser, J. M., Reiss, D., Lichtenstein, P., Spotts, E. L., & Ganiban, J. (2007). Father-adolescent relationships and the role of genotype-environment correlation. Journal of Family Psychology, 21(4), 560. https://doi.org/10.1037/0893-3200.21.4.560 CrossRefGoogle ScholarPubMed
Neiderhiser, J. M., Reiss, D., Pedersen, N. L., Lichtenstein, P., Spotts, E. L., Hansson, K., Cederblad, M., & Elthammer, O. (2004). Genetic and environmental influences on mothering of adolescents: A comparison of two samples. Developmental Psychology, 40(3), 335. https://doi.org/10.1037/0012-1649.40.3.335 CrossRefGoogle ScholarPubMed
O’Reilly, P., Choi, S., Garcia-Gonzalez, J., Ruan, Y., Wu, H. M., Johnson, J., & Hoggart, C. (2021). The power of pathway-based polygenic risk scores. Europe PMC. https://doi.org/10.21203/rs.3.rs-643696/v1 Google Scholar
Obel, C., Olsen, J., Henriksen, T. B., Rodriguez, A., Järvelin, M. R., Moilanen, I., Parner, E., Linnet, K. M., Taanila, A., Ebeling, H., & Heiervang, E. (2011). Is maternal smoking during pregnancy a risk factor for hyperkinetic disorder?—Findings from a sibling design. International Journal of Epidemiology, 40(2), 338–345. https://doi.org/10.1093/ije/dyq185 CrossRefGoogle ScholarPubMed
Peyre, H., Schoeler, T., Liu, C., Williams, C. M., Hoertel, N., Havdahl, A., & Pingault, J. B. (2021). Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder. Journal of Child Psychology and Psychiatry, 62(11), 1285–1296. https://doi.org/10.1101/2020.04.22.054825 CrossRefGoogle ScholarPubMed
Pingault, D. J. B., Cecil, C. A. M., Murray, J., Munafò, M. R., & Viding, E. (2017). Causal inference in psychopathology: A systematic review of Mendelian randomisation studies aiming to identify environmental risk factors for psychopathology. Psychopathology Review, a4(1), 4–25. https://doi.org/10.5127/pr.038115 CrossRefGoogle Scholar
Pingault, J. B., O’Reilly, P. F., Schoeler, T., Ploubidis, G. B., Rijsdijk, F., & Dudbridge, F. (2018). Using genetic data to strengthen causal inference in observational research. Nature Reviews Genetics, 9, 566–580. https://doi.org/10.1038/s41576-018-0020-3 CrossRefGoogle Scholar
Pingault, J. B., Viding, E., Galéra, C., Greven, C. U., Zheng, Y., Plomin, R., & Rijsdijk, F. (2015). Genetic and environmental influences on the developmental course of attention-deficit/hyperactivity disorder symptoms from childhood to adolescence. JAMA Psychiatry, 72(7), 651–658. https://doi.org/10.1001/jamapsychiatry.2015.0469 CrossRefGoogle ScholarPubMed
Pingault, J.-B., Barkhuizen, W., Wang, B., Hannigan, L. J., Eilertsen, E. M., Andreassen, O. A., Ask, H., Tesli, M., Askeland, R. B., Smith, G. D., Davies, N., Reichborn-Kjennerud, T., Ystrom, E., & Havdahl, A (2021). Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort. MedRxiv, 19(2), 175. https://doi.org/10.1101/2021.02.16.21251737.Google Scholar
Plomin, R. (1990). Nature and nurture: An introduction to human behavioral genetics. Nature and nurture: An introduction to human behavioral genetics. Thomson Brooks/Cole Publishing Co.Google Scholar
Polderman, T. J. C., Benyamin, B., De Leeuw, C. A., Sullivan, P. F., Van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics, 47(7), 702–709. https://doi.org/10.1038/ng.3285 CrossRefGoogle ScholarPubMed
Price, T. S., & Jaffee, S. R. (2008). Effects of the family environment: Gene-environment interaction and passive gene-environment correlation. Developmental Psychology, 44(2), 305. https://doi.org/10.1037/0012-1649.44.2.305 CrossRefGoogle ScholarPubMed
Rees, E., O’Donovan, M. C., & Owen, M. J. (2015). Genetics of schizophrenia. Current Opinion in Behavioral Sciences, 2, 8–14. https://doi.org/10.1016/j.cobeha.2014.07.001 CrossRefGoogle Scholar
Reiss, D., Leve, L. D., & Neiderhiser, J. M. (2013). How genes and the social environment moderate each other. American Journal of Public Health, 103(S1), S111–S121. https://doi.org/10.2105/AJPH.2013.301408 CrossRefGoogle ScholarPubMed
Rhea, S. A., Bricker, J. B., Wadsworth, S. J., & Corley, R. P. (2013). The Colorado adoption project. Twin Research and Human Genetics, 16(1), 358–365. https://doi.org/10.1017/thg.2012.109 CrossRefGoogle ScholarPubMed
Rice, F., Langley, K., Woodford, C., Davey Smith, G., & Thapar, A. (2018). Identifying the contribution of prenatal risk factors to offspring development and psychopathology: What designs to use and a critique of literature on maternal smoking and stress in pregnancy. Development and Psychopathology, 30(3), 1107–1128. https://doi.org/10.1017/S0954579418000421 CrossRefGoogle Scholar
Rice, F., Riglin, L., Thapar, A. K., Heron, J., Anney, R., O’Donovan, M. C., & Thapar, A. (2019). Characterizing developmental trajectories and the role of neuropsychiatric genetic risk variants in early-onset depression. JAMA Psychiatry, 76(3), 306–313. https://doi.org/10.1001/jamapsychiatry.2018.3338 CrossRefGoogle ScholarPubMed
Riglin, L., Leppert, B., Dardani, C., Thapar, A. K., Rice, F., O’donovan, M. C., Smith, G. D, Stergiakouli, E., Tilling, K., & Thapar, A. (2021). ADHD and depression: Investigating a causal explanation. Psychological Medicine, 51(11), 1890–1897. https://doi.org/10.1017/S0033291720000665 CrossRefGoogle ScholarPubMed
Rutter, M. (2000). Genetic studies of autism: From the, 1970s, into the millennium. Journal of Abnormal Child Psychology, 28(1), 3–14. https://doi.org/10.1023/A:1005113900068 CrossRefGoogle ScholarPubMed
Rutter, M. (2004). Pathways of genetic influences on psychopathology. European Review, 12(1), 19–33. https://doi.org/10.1017/S1062798704000031 CrossRefGoogle Scholar
Rutter, M. (2007a). Gene-environment interdependence. Developmental Science, 10(1), 12–18. https://doi.org/10.1111/j.1467-7687.2007.00557.x CrossRefGoogle ScholarPubMed
Rutter, M. (2007b). Proceeding from observed correlation to causal inference: The use of natural experiments. Perspectives on Psychological Science: A Journal of the Association for Psychological Science, 2(4), 377–395. https://doi.org/10.1111/j.1745-6916.2007.00050.x CrossRefGoogle ScholarPubMed
Rutter, M. (2012). Gene-environment interdependence. European Journal of Developmental Psychology, 9(4), 391–412. https://doi.org/10.1080/17405629.2012.661174 CrossRefGoogle Scholar
Rutter, M. (2015). Some of the complexities involved in gene-environment interplay. International Journal of Epidemiology, 44(4), 1128–1129. https://doi.org/10.1093/ije/dyv054 CrossRefGoogle ScholarPubMed
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(3-4), 226–261. https://doi.org/10.1111/j.1469-7610.2005.01557.x CrossRefGoogle ScholarPubMed
Rutter, M. L., & Thapar, A. (2016). Using natural experiments to test environmental mediation hypotheses. In Cicchetti, D. (Ed.), Developmental psychopathology: Theory and method (Vol. 1, 3rd ed., pp. 129–155). John Wiley & Sons, Inc.Google Scholar
Scarr, S., & McCartney, K. (1983). How people make their own environments: A theory of genotype→ environment effects. Child Development, 54(2), 424–435. https://doi.org/10.2307/1129703 Google Scholar
Schoeler, T., Choi, S. W., Dudbridge, F., Baldwin, J., Duncan, L., Cecil, C. M., Walton, E., Viding, E., McCrory, E., & Pingault, J. B. (2019). Multi-polygenic score approach to identifying individual vulnerabilities associated with the risk of exposure to bullying. JAMA Psychiatry, 76(7), 730–738. https://doi.org/10.1001/jamapsychiatry.2019.0310 CrossRefGoogle ScholarPubMed
Sellers, R., Harold, G. T., Thapar, A., Neiderhiser, J. M., Ganiban, J. M., Reiss, D., Shaw, D. S., Natsuaki, M. N., & Leve, L. D. (2020). Examining the role of genetic risk and longitudinal transmission processes underlying maternal parenting and psychopathology and children’s ADHD symptoms and aggression: Utilizing the advantages of a prospective adoption design. Behavior Genetics, 50(4), 247–262. https://doi.org/10.1007/s10519-020-10006-y CrossRefGoogle ScholarPubMed
Sellers, R., Smith, A., Leve, L. D., Nixon, E., Cane, T. C., Cassell, J., & Harold, G. (2019). Utilising genetically informed research designs to better understand family processes and child development: Implications for adoption and foster care focused interventions. Adoption & Fostering, 43(3), 351–371. https://doi.org/10.1177/0308575919866526 CrossRefGoogle ScholarPubMed
Shanahan, M. J., & Hofer, S. M. (2005). Social context in gene-environment interactions: Retrospect and prospect. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 60(Special_Issue_1), 65–76. https://doi.org/10.1093/geronb/60.Special_Issue_1.65 CrossRefGoogle ScholarPubMed
Singh, T., Poterba, T., Curtis, D., Akil, H., Al Eissa, M., Barchas, J. D., Bass, N., Bigdeli, T. B., Breen, G., Bromet, E. J., & Buckley, P. F. (2022). Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature, 604, 509–516. https://doi.org/10.1038/s41586-022-04556-w CrossRefGoogle ScholarPubMed
Smith, G. D., & Hemani, G. (2014). Mendelian randomization: Geneticanchorsfor causal inference in epidemiological studies. Human Molecular Genetics, 23(R1), R89–R98. https://doi.org/10.1093/hmg/ddu328 CrossRefGoogle Scholar
Smith, G. D., Richmond, R. C., & Pingault, J. B. Eds (2021). Combining human genetics and causal inference to understand human disease and development. Cold Spring Harbor Laboratory Press.Google Scholar
Smoller, J. W. (2019, August 1). Psychiatric genetics begins to find its footing. American Journal of Psychiatry, 176, 609–614. https://doi.org/10.1176/appi.ajp.2019.19060643 CrossRefGoogle ScholarPubMed
State, M. W., & Thapar, A. (2015). Genetics. In Rutter’s child and adolescent psychiatry (pp. 303–316). John Wiley & Sons, Ltd. https://doi.org/10.1002/9781118381953.ch24 CrossRefGoogle Scholar
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Borglum, A. D., Breen, G., Cichon, S, Edenberg, H. J., Faraone, S. V., Gelernter, J., & Mathews, C. A. (2018). Psychiatric genomics: An update and an agenda. The American Journal of Psychiatry, 175(1), 15–27. https://doi.org/10.1176/appi.ajp.2017.17030283 CrossRefGoogle Scholar
Sullivan, P. F., & Geschwind, D. H. (2019). Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell, 177(1), 162–183. https://doi.org/10.1016/j.cell.2019.01.015 CrossRefGoogle ScholarPubMed
Tenesa, A., & Haley, C. S. (2013, February). The heritability of human disease: Estimation, uses and abuses. Nature Reviews Genetics, 14(2), 139–149. https://doi.org/10.1038/nrg3377 CrossRefGoogle ScholarPubMed
TenEyck, M., & Barnes, J. C. (2015). Examining the impact of peer group selection on self-reported delinquency: A consideration of active gene-environment correlation. Criminal Justice and Behavior, 42(7), 741–762. https://doi.org/10.1177/0093854814563068 CrossRefGoogle Scholar
Thapar, A. (2018). Discoveries on the genetics of ADHD in the 21st century: New findings and their implications. American Journal of Psychiatry, 175(10), 943–950. https://doi.org/10.1176/APPI.AJP.2018.18040383 CrossRefGoogle ScholarPubMed
Thapar, A., Harold, G., Rice, F., Ge, X., Boivin, J., Hay, D., van den Bree, M, & Lewis, A. (2007). Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects. BMC Medical Research Methodology, 7(1), 1–8. https://doi.org/10.1186/1471-2288-7-25 CrossRefGoogle ScholarPubMed
Thapar, A., & Rice, F. (2020). Family-Based designs that disentangle inherited factors from pre-and postnatal environmental exposures: in vitro fertilization, discordant sibling pairs, maternal versus paternal comparisons, and adoption designs. Cold Spring Harbor Perspectives in Medicine, a038877.Google Scholar
Thapar, A., & Rice, F. (2021). Family-based designs that disentangle inherited factors from pre-and postnatal environmental exposures: In vitro fertilization, discordant sibling pairs, maternal versus paternal comparisons, and adoption designs. Cold Spring Harbor Perspectives in Medicine, 11(3), 1–15. https://doi.org/10.1101/cshperspect.a038877 CrossRefGoogle ScholarPubMed
Thapar, A., Rice, F., Hay, D., Boivin, J., Langley, K., van den Bree, M., Rutter, M., & Harold, G. (2009). Prenatal smoking might not cause attention-deficit/hyperactivity disorder: Evidence from a novel design. Biological Psychiatry, 66(8), 722–727. https://doi.org/10.1016/j.biopsych.2009.05.032 CrossRefGoogle Scholar
Thapar, A., & Rutter, M. (2015). Using natural experiments and animal models to study causal hypotheses in relation to child mental health problems. In: Rutter’s child and adolescent psychiatry (pp. 143–162). Wiley. https://doi.org/10.1002/9781118381953.ch12 CrossRefGoogle Scholar
Thapar, A., & Rutter, M. (2019). Do natural experiments have an important future in the study of mental disorders? Psychological Medicine, 49(7), 1079–1088. https://doi.org/10.1017/S0033291718003896 CrossRefGoogle Scholar
Thapar, A., & Rutter, M. (2021). Genetic advances in autism. Journal of Autism and Developmental Disorders, 51(12), 4321–4332. https://doi.org/10.1007/s10803-020-04685-z CrossRefGoogle ScholarPubMed
Thompson, W. D. (1991). Effect modification and the limits of biological inference from epidemiologic data. Journal of Clinical Epidemiology, 44(3), 221–232. https://doi.org/10.1016/0895-4356(91)90033-6 CrossRefGoogle ScholarPubMed
Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C. Y., Dennison, C. A., Hall, L. S., & Lam, M. (2022). Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature, 604, 502–508. https://doi.org/10.1038/s41586-022-04434-5 CrossRefGoogle ScholarPubMed
Turkheimer, E., Haley, A., Waldron, M., D’Onofrio, B., & Gottesman, I. I. (2003). Socioeconomic status modifies heritability of IQ in young children. Psychological Science, 14(6), 623–628. https://doi.org/10.1046/j.0956-7976.2003.psci_1475.x CrossRefGoogle ScholarPubMed
Uher, R., & Zwicker, A. (2017). Etiology in psychiatry: Embracing the reality of poly-gene-environmental causation of mental illness. World Psychiatry, 16(2), 121–129. https://doi.org/10.1002/wps.20436 CrossRefGoogle ScholarPubMed
Verlouw, J. A., Clemens, E., de Vries, J. H., Zolk, O., Verkerk, A. J., am Zehnhoff-Dinnesen, A., Medina-Gomez, C., Lanvers-Kaminsky, C., Rivadeneira, F., Langer, T., & van Meurs, J. B. (2021). A comparison of genotyping arrays. European Journal of Human Genetics, 29(11), 1611–1624. https://doi.org/10.1038/s41431-021-00917-7 CrossRefGoogle ScholarPubMed
Visscher, P. M., & Yang, J. (2016). A plethora of pleiotropy across complex traits. Nature Genetics, 48(7), 707–708. https://doi.org/10.1038/ng.3604 CrossRefGoogle ScholarPubMed
Vissers, L. E. L. M., Gilissen, C., & Veltman, J. A. (2016). Genetic studies in intellectual disability and related disorders. Nature Reviews Genetics, 17, 9–18. https://doi.org/10.1038/nrg3999 CrossRefGoogle ScholarPubMed
Vitaro, F., Beaver, K. M., Brendgen, M., Dickson, D. J., Dionne, G., & Boivin, M. (2021). A genetically-controlled, cross-lagged study of the association between friends’ deviance and participants’ delinquency during adolescence: A replication. Developmental Psychology, 57(12), 2011–2021. https://doi.org/10.1037/dev0001181.CrossRefGoogle ScholarPubMed
Wang, B., Baldwin, J. R., Schoeler, T., Cheesman, R., Barkhuizen, W., Dudbridge, F., Bann, D., Morris, T. T., & Pingault, J. B. (2021). Robust genetic nurture effects on education: A systematic review and meta-analysis based on 38,654 families across 8 cohorts. American Journal of Human Genetics, 108(9), 1780–1791. https://doi.org/10.1016/j.ajhg.2021.07.010 CrossRefGoogle ScholarPubMed
Warrier, V., Kwong, A. S., Luo, M., Dalvie, S., Croft, J., Sallis, H. M., Baldwin, J., Munafò, M. R., Nievergelt, C. M., Grant, A. J., & Burgess, S. (2021). Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: A genetically informed approach. The Lancet Psychiatry, 8(5), 373–386. https://doi.org/10.1016/S2215-0366(20)30569-1 CrossRefGoogle ScholarPubMed
Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. M., & Bacanu, S. A. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668–681. https://doi.org/10.1038/s41588-018-0090-3 CrossRefGoogle ScholarPubMed
Zammit, S., Owen, M. J., & Lewis, G. (2010). Misconceptions about gene-environment interactions in psychiatry. Evidence-Based Mental Health, 13(3), 65–68. https://doi.org/10.1136/ebmh1056 CrossRefGoogle ScholarPubMed
Zhang, X., & Belsky, J. (2022). Three phases of Gene× Environment interaction research: Theoretical assumptions underlying gene selection. Development and Psychopathology, 34(1), 295–306. https://doi.org/10.1017/S0954579420000966 CrossRefGoogle ScholarPubMed