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Naturalistic Experimental Designs as Tools for Understanding the Role of Genes and the Environment in Prevention Research

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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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Correspondence to Leslie D. Leve.

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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.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

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.

Informed Consent

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).

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