Abstract
Before genetic approaches were applied in experimental studies with human populations, they were used by animal and plant breeders to observe, and experimentally manipulate, the role of genes and environment on specific phenotypic or behavioral outcomes. For obvious ethical reasons, the same level of experimental control is not possible in human populations. Nonetheless, there are natural experimental designs in human populations that can serve as logical extensions of the rigorous quantitative genetic experimental designs used by animal and plant researchers. Applying concepts such as cross-fostering and common garden rearing approaches from the life science discipline, we describe human designs that can serve as naturalistic proxies for the controlled quantitative genetic experiments facilitated in life sciences research. We present the prevention relevance of three such human designs: (1) children adopted at birth by parents to whom they are not genetically related (common garden approach); (2) sibling designs where one sibling is reared from birth with unrelated adoptive parents and the other sibling is reared from birth by the biological mother of the sibling pair (cross-fostering approach); and (3) in vitro fertilization designs, including egg donation, sperm donation, embryo donation, and surrogacy (prenatal cross-fostering approach). Each of these designs allows for differentiation of the effects of the prenatal and/or postnatal rearing environment from effects of genes shared between parent and child in naturalistic ways that can inform prevention efforts. Example findings from each design type are provided and conclusions drawn about the relevance of naturalistic genetic designs to prevention science.
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References
Baumrind, D. (1971). Current patterns of parental authority. Developmental Psychology, 4, 1–103.
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885–908. doi:10.1037/a0017376.
Bouchard, T. J., Lykken, D. T., McGue, M., Segal, N. L., & Tellegen, A. (1990). Sources of human psychological differences: The Minnesota study of twins reared apart. Science, 250, 223–228. doi:10.1126/science.2218526.
Brody, G. H., Yu, T., Chen, Y. F., Kogan, S. M., Evans, G. W., Windle, M., … & Philibert, R. A. (2013). Supportive family environments, genes that confer sensitivity, and allostatic load among rural African American emerging adults: A prospective analysis. Journal of Family Psychology, 27, 22–29. doi:10.1037/a0027829.
Cadoret, R. J., Yates, W. R., Woodworth, G., & Stewart, M. A. (1995). Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Archives of General Psychiatry, 52, 916–924. doi:10.1001/archpsyc.1995.03950230030006.
Cho, I., & Blaser, M. J. (2012). The human microbiome: At the interface of health and disease. Nature Reviews Genetics, 13, 260–270. doi:10.1038/nrg3182.
Darwin, C. (1859). On the origin of the species by natural selection. London: Murray.
Dick, D. M., Meyers, J. L., Latendresse, S. J., Creemers, H. E., Lansford, J. E., Pettit, G. S., … & Buitelaar, J. K. (2011). CHRM2, Parental monitoring, and adolescent externalizing behavior evidence for gene-environment interaction. Psychological Science, 22, 481–489. doi:10.1177/0956797611403318.
Eley, T. C., McAdams, T. A., Rijsdijk, F. V., Lichtenstein, P., Narusyte, J., Reiss, D., Spotts, E. L., Ganiban, J. M., & Neiderhiser, J. M. (2015). The intergenerational transmission of anxiety: A children-of-twins study. American Journal of Psychiatry, 172, 630–637. doi:10.1176/appi.ajp.2015.14070818.
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & Van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 7–28. doi:10.1017/S0954579410000611.
Falconer, D., & Mackay, T. (1996). Introduction to quantitative genetics. London: Prentice Hall.
Fisher, R. A. (1918). The correlation between relatives on the supposition of Mendelian inheritance. Philosophical Transactions of the Royal Society of Edinburgh, 52, 399–433. doi:10.1017/S0080456800012163.
Foster, J. A., & Neufeld, K.-A. (2013). Gut–brain axis: How the microbiome influences anxiety and depression. Trends in Neurosciences, 36, 305–312. doi:10.1016/j.tins.2013.01.005.
Franzosa, E. A., Huang, K., Meadow, J. F., Gevers, D., Lemon, K. P., Bohannan, B. J., & Huttenhower, C. (2015). Identifying personal microbiomes using metagenomic codes. Proceedings of the National Academy of Sciences, 112, E2930–E2938. doi:10.1073/pnas.1423854112.
Galton, F. (1883). Inquiries into human faculty and its development. London: Macmillan.
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, 574–589. doi:10.1037/0012-1649.32.4.574.
Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, M. A., Knight, R., Ober, C., … & Ley, R. E. (2016). Genetic determinants of the gut microbiome in UK Twins. Cell Host & Microbe, 19, 731–743. doi:10.1016/j.chom.2016.04.017.
Grice, E. A., & Segre, J. A. (2012). The human microbiome: Our second genome. Annual Review of Genomics and Human Genetics, 13, 151–170. doi:10.1146/annurev-genom-090711-163814.
Harold, G. T., Rice, F., Hay, D. F., Boivin, J., Van Den Bree, M., & Thapar, A. (2011). Familial transmission of depression and antisocial behavior symptoms: Disentangling the contribution of inherited and environmental factors and testing the mediating role of parenting. Psychological Medicine, 41, 1175–1185. doi:10.1017/S0033291710001753.
Harold, G. T., Leve, L. D., Barrett, D., Elam, K., Neiderhiser, J. M., Natsuaki, M. N., …& 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, 54, 1038–1046. doi:10.1111/jcpp.12100.
Hershberger, S. L. (1994). Genotype-environment interaction and correlation. In J. C. DeFries, R. Plomin, & D. W. Fulker (Eds.), Nature and nurture during middle childhood (pp. 281–294). Malden: Blackwell.
Horwitz, B. N., & Neiderhiser, J. M. (Eds.). (2015). Behavioral genetics of interpersonal relationships across the lifespan. New York: Springer.
Kendler, K. S., Walters, E. E., Neale, M. C., Kessler, R. C., Heath, A. C., & Eaves, L. J. (1995). The structure of the genetic and environmental risk factors for six major psychiatric disorders in women: Phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Archives of General Psychiatry, 52, 374–383.
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2016). The rearing environment and risk for drug abuse: A Swedish national high-risk adopted and not adopted co-sibling control study. Psychological Medicine, 46, 1359–1366. doi:10.1017/S0033291715002858.
Klahr, A. M., & Burt, S. A. (2014). Elucidating the etiology of individual differences in parenting: A meta-analysis of behavioral genetic research. Psychological Bulletin, 140, 544–586. doi:10.1037/a0034205.
Lemery-Chalfant, K., Kao, K., Swann, G., & Goldsmith, H. H. (2013). Childhood temperament: Passive gene–environment correlation, gene–environment interaction, and the hidden importance of the family environment. Development and Psychopathology, 25, 51–63. doi:10.1017/S0954579412000892.
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 and Adolescent Psychiatry, 48, 1102–1109. doi:10.1097/CHI.0b013e3181b8bfc0.
Leve, L. D., Kerr, D., Shaw, D., Ge, X., Neiderhiser, J. M., Reid, J. B., …& Reiss, D. (2010). Infant pathways to externalizing behavior: Evidence of genotype x environment interaction. Child Development, 81, 340–356.
Leve, L. D., Neiderhiser, J. M., Shaw, D. S., Ganiban, J., Natsuaki, M. N., & Reiss, D. (2013). The early growth and development study: A prospective adoption study of child behavior from birth through middle childhood. Twin Research and Human Genetics, 16, 412–423. doi:10.1017/thg.2012.126.
Lunkenheimer, E. S., Dishion, T. J., Shaw, D. S., Connell, A. M., Gardner, F., Wilson, M. N., & Skuban, E. M. (2008). Collateral benefits of the family check-up on early childhood school readiness: Indirect effects of parents’ positive behavior support. Developmental Psychology, 44, 1737–1752.
Mackay, T. F. C. (2001). The genetic architecture of quantitative traits. Annual Review of Genetics, 35, 303–339. doi:10.1146/annurev.genet.35.102401.090633.
Meadow, J. F., Altrichter, A. E., Bateman, A. C., Stenson, J., Brown, G. Z., Green, J. L., & Bohannan, B. J. (2015). Humans differ in their personal microbial cloud. PeerJ, 3, e1258.
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161–1192. doi:10.1146/annurev.neuro.24.1.1161.
Mednick, S. A., Gabrielli, W. F., & Hutchings, B. (1984). Genetic influences in criminal convictions: Evidence from an adoption cohort. Science, 224, 891–894.
Mendel, G. (1863). Experiments in plant hybridization. Cambridge: Cambridge University Press.
Mulle, J. G., Sharp, W. G., & Cubells, J. F. (2013). The gut microbiome: A new frontier in autism research. Current Psychiatry Reports, 15, 1–9. doi:10.1007/s11920-012-0337-0.
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, 560–571. doi:10.1037/0893-3200.21.4.560.
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.
Pedersen, N. L., McClearn, G. E., Plomin, R., Nesselroade, J. R., Berg, S., & DeFaire, U. (1991). The Swedish adoption twin study of aging: An update. Acta Geneticae Medicae et Gemellologiae: Twin Research, 40, 7–20. doi:10.1017/S0001566000006681.
Plomin, R., & DeFries, J. C. (1983). The Colorado adoption project. Child Development, 54, 276–289. doi:10.2307/1129691.
Rhea, S. A., Bricker, J. B., Wadsworth, S. J., & Corley, R. P. (2013). The Colorado adoption project. Twin Research and Human Genetics, 16, 358–365. doi:10.1017/thg.2012.109.
Rice, F., Harold, G. T., Boivin, J., Hay, D. F., van den Bree, M., & Thapar, A. (2009). Disentangling prenatal and inherited influence in humans with an experimental design. Proceedings of the National Academy of Sciences, 16, 2464–2467. doi:10.1073/pnas.0808798106.
Rutter, M., Pickles, A., Murray, R., & Eaves, L. (2001). Testing hypotheses on specific environmental causal effects on behavior. Psychological Bulletin, 127, 291–324.
Sale, M., Mychaleckyj, J., & Chen, W. (2009). Planning and executing a genome wide association study (GWAS). Molecular Endocrinology: Methods and Protocols, 590, 403–418. doi:10.1007/978-1-60327-378-7_25.
Schiff, M., Duyme, M., Dumaret, A., & Tomkiewicz, S. (1982). How much could we boost scholastic achievement and IQ scores? A direct answer from a French adoption study. Cognition, 12, 165–196. doi:10.1016/0010-0277(82)90011-7.
Sorensen, T. I., Price, R. A., Stunkard, A. J., & Schulsinger, F. (1989). Genetics of obesity in adult adoptees and their biological siblings. British Medical Journal, 298, 87–90.
Thapar, A., Harold, G., Rice, F., Ge, X., Boivin, J., Hay, D., … & 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, 1-8. doi:10.1186/1471-2288-7-25.
Zeng, Z. B., Kao, C. H., & Basten, C. J. (1999). Estimating the genetic architecture of quantitative traits. Genetical Research, 74, 279–289. doi:10.1017/S0016672399004255.
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Funding for this work was provided by R01 DA035062, P50 DA035763, and R01 DA020585 from NIDA; R01 HD042608 and R56 HD042608 from NICHD; UG3 OD023389 from the Office of the Director; and R24 GM079486 and P50 GM098911 from NIGMS, U.S. PHS. Funding was also provided by DEB 0949053 and IOS 102728 from NSF, from a Wellcome Trust Showcase Award, a Wellcome Trust Project grant, a Project Grant award from the Nuffield Foundation, and ES/L014718/1 from the Economic and Social Research Council. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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This is a review article and no original research was conducted for this manuscript. The original studies described in this manuscript that were led by the current authors (EGDS, EPoCh, and Cardiff IVF Study) received approval from their respective Institutional Review Boards. All procedures performed in these three studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
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No original research was conducted in the course of this work. Informed consent was obtained from all individual participants included in the three studies described in this manuscript that were led by the current authors (EGDS, EPoCh, and Cardiff IVF Study).
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Leve, L.D., Neiderhiser, J.M., Harold, G.T. et al. Naturalistic Experimental Designs as Tools for Understanding the Role of Genes and the Environment in Prevention Research. Prev Sci 19, 68–78 (2018). https://doi.org/10.1007/s11121-017-0746-8
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DOI: https://doi.org/10.1007/s11121-017-0746-8