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Review
. 2021 Mar 1;11(3):a038877.
doi: 10.1101/cshperspect.a038877.

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

Anita Thapar  1 , Frances Rice  1
Affiliations
Review

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

Anita Thapar et al. Cold Spring Harb Perspect Med. .

Abstract

Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. We focus on prenatal exposures. We highlight that the family-based designs that can separate the prenatal environment from inherited confounds are different to those that are able to pull apart later-life environmental exposures from inherited confounds. We provide a brief review of the literature on maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) and conduct problems; these inconsistencies in the literature make a review useful and this illustrates that results of family-based genetically informed studies are inconsistent with a causal interpretation for this exposure and these two offspring outcomes.

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Figures

Figure 1.
Figure 1.
Environmental exposures and child outcome: passive gene–environment correlation, dynastic, and exposure effects. Shown is a schematic of passive gene–environment correlation for prenatal environmental exposures in the absence of assortative mating. “p” represents passive gene–environment correlation (i.e., where association between an exposure comes about because of shared inherited influences on environmental exposure in the parent generation and child outcome in the offspring generation) (pf denotes paternal effects and pm denotes maternal effects). “e” represents a direct environmental exposure effect on offspring outcome (ef denotes paternal effects and em denotes maternal effects). “d” represents the influence of nature on nurture (i.e., where parental inherited characteristics influence environmental exposures that may impact on offspring). The product of d and e gives an estimate of what have been termed “dynastic effects” where parental alleles may influence environmental exposure but the environment then has a direct impact on offspring independent of alleles shared between parent and offspring. (gf) father genes, (gm) mother genes, (gc) child genes.
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