This essay examines the origin of genotype-environment interaction, or G×E. "Origin" and not "the origin" because the thesis is that there were actually two distinct concepts of G×E at this beginning: a biometric concept, or \[G \times E_B\], and a developmental concept, or \[G \times E_D \]. R. A. Fisher, one of the founders of population genetics and the creator of the statistical analysis of variance, introduced the biometric concept as he attempted to resolve one of the (...) main problems in the biometric tradition of biology - partitioning the relative contributions of nature and nurture responsible for variation in a population. Lancelot Hogben, an experimental embryologist and also a statistician, introduced the developmental concept as he attempted to resolve one of the main problems in the developmental tradition of biology - determining the role that developmental relationships between genotype and environment played in the generation of variation. To argue for this thesis, I outline Fisher and Hogben's separate routes to their respective concepts of G × E; then these separate interpretations of G × E are drawn on to explicate a debate between Fisher and Hogben over the importance of G × E, the first installment of a persistent controversy. Finally, Fisher's \[G \times E_B\] and Hogben's \[G \times E_D \] are traced beyond their own work into mid-2Oth century population and developmental genetics, and then into the infamous IQ Controversy of the 1970s. (shrink)

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype–environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype–environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as (...) a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms. (shrink)

Numerous studies have demonstrated that both catechol- O -methyltransferase ( COMT ) gene and monoamine oxidase A ( MAOA ) gene have been involved in aggressive behavior, as have stressful life events (SLEs). However, most of available evidence was based upon single gene or single gene–environment design, which is limited in accounting for the variance of aggressive behavior, a complex phenotype. This study examined the possible gene × gene × environment interactions between SLE (interpersonal problems and academic pressure) (...) and two genetic polymorphisms ( MAOA T941G and COMT Ala22/72Ser) correlated with aggressive behaviors in a sample of 658 Chinese male adolescents. Mothers and teachers reported on adolescents’ aggressive behavior using Achenbach’s Child Behavior Checklist and Teacher Report Form, respectively. Adolescents completed Self-Rating Life Events Checklist. Saliva samples were collected for DNA analysis. The results revealed no main effects of MAOA T941G and COMT Ala22/72Ser polymorphisms on male adolescents’ aggressive behaviors. However, a two-way interactive effect of interpersonal problems and MAOA T941G genotype on teacher-reported aggressive behavior was observed: adolescents with lower activity of MAOA T allele, but not those with MAOA G allele, exhibited greater aggressive behavior with an increase in interpersonal problems. A three-way interaction among COMT Ala22/72Ser and MAOA T941G polymorphisms, and SLE in the academic pressure on aggressive behavior was also identified. Among adolescents with lower activity of COMT GT/TT genotype and MAOA T allele, the higher level of academic pressure was significantly linked with an amplification of aggressive behavior, whereas this association didn’t exist among those with other genotypes. The present study presents the first evidence of COMT × MAOA × SLE interaction effect on male adolescents’ aggressive behavior, highlights the importance of considering distinct domains of stressful events and information bias when examining the effect of MAOA and COMT on aggressive behavior, and thereby contributes to MAOA gene-aggression and COMT gene-aggression literature. (shrink)

Quantitative genetics (QG) analyses variation in traits of humans, other animals, or plants in ways that take account of the genealogical relatedness of the individuals whose traits are observed. “Classical” QG, where the analysis of variation does not involve data on measurable genetic or environmental entities or factors, is reformulated in this article using models that are free of hypothetical, idealized versions of such factors, while still allowing for defined degrees of relatedness among kinds of individuals or “varieties.” The gene (...) - free formulation encompasses situations encountered in human QG as well as in agricultural QG. This formulation is used to describe three standard assumptions involved in classical QG and provide plausible alternatives. Several concerns about the partitioning of trait variation into components and its interpretation, most of which have a long history of debate, are discussed in light of the gene-free formulation and alternative assumptions. That discussion is at a theoretical level, not dependent on empirical data in any particular situation. Additional lines of work to put the gene-free formulation and alternative assumptions into practice and to assess their empirical consequences are noted, but lie beyond the scope of this article. The three standard QG assumptions examined are: (1) partitioning of trait variation into components requires models of hypothetical, idealized genes with simple Mendelian inheritance and direct contributions to the trait; (2) all other things being equal, similarity in traits for relatives is proportional to the fraction shared by the relatives of all the genes that vary in the population (e.g., fraternal or dizygotic twins share half of the variable genes that identical or monozygotic twins share); (3) in analyses of human data, genotype-environment interaction variance (in the classical QG sense) can be discounted. The concerns about the partitioning of trait variation discussed include: the distinction between traits and underlying measurable factors; the possible heterogeneity in factors underlying the development of a trait; the kinds of data needed to estimate key empirical parameters; and interpretations based on contributions of hypothetical genes; as well as, in human studies, the labeling of residual variance as a non-shared environmental effect; and the importance of estimating interaction variance. (shrink)

The target article approaches individual differences in terms of phenotypic differences developing through the interaction between a specific genetic make up and environmental variables. This interaction is proposed to be cooperative and oriented toward a progressive stabilisation of the trait. However, experimental data from animal studies indicate that environmental pressure promotes dramatic changes in phenotypic expression in mature organisms. Indeed, environmental constraint not only promotes the phenotypic expression of facilitated VTA-NAS DA transmission in genotype-resistant individuals; it also (...) inhibits its expression in genetically prone individuals. This is in line with negative genotype-environment correlation revealed by behavior genetics. (shrink)

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between (...) the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. (shrink)

The ArgumentMany associations have recently been discovered between phenotypic variation and genetic loci, causing some to advocate what Robert Sinsheimer has called “a new eugenics” that would treat genetic “defects” in individuals prone to a disease. The first premise of this vision is that genetic association studies reveal the biological cause of the phenotypic variation. Once the responsible genes are known, the second premise is that we should focus upon changing “nature” rather than “nurture” by correcting the “defective” genes.The first (...) premise is flawed because associations between genetic markers and phenotypes can be spurious, as shown by an example. Moreover, it is shown that using non-causative but associated genetic markers one at a time (the normal practice) can lead to incorrect predictions of disease risk for many individuals. Going from association to causation is a non-trivial step scientifically that has rarely been done in much of the human genetic research.Even when a particular locus does contribute to the phenotypic variation of interest, the first premise remains flawed because phenotypes in general arise from complex interactions among genes and between genes and environments as shown for genes associations with coronary artery disease (CAD). The ability of current molecular genetic tools to “fix” defective genotypes is extremely limited, but even if the technological problems could be overcome, the studies on CAD reveal no obvious “defective” gene to fix because the genetic effects are so context dependent (upon both other genes and environmental factors). Contrary to the second premise of the new eugenics, the more we learn about how different genotypes show variable responses to environments, themoreimportant the environment becomes for individual treatment.The paradigm of a “defective gene” may work for classical Mendelian genetic diseases that are due to loss-of-function mutations. However, such mutations affect only a small portion of humanity. When the focus is changed to common disease and behavioral phenotypes, the “defective gene” paradigm is biologically meaningless and often harmful when applied to individuals. Thus, even when genes clearly do influence common phenotypic variation, the premises of the “new eugenics” are biologically indefensible. (shrink)

The critics of "hereditarianism" often claim that any attempt to explain human behavior by invoking genes is confronted with insurmountable methodological difficulties. They reject the idea that heritability estimates could lead to genetic explanations by pointing out that these estimates are strictly valid only for a given population and that they are exposed to the irremovable confounding effects of genotype-environment interaction and genotype-environment correlation. I argue that these difficulties are greatly exaggerated, and that we would (...) be wrong to regard them as presenting a fundamental obstacle to the search for genetic explanations. I also show that, to the extent they are cogent, these objections may prove to be even more damaging to the "environmentalist" standpoint. (shrink)

A standard norm of reaction (NoR) is a graphical depiction of the phenotypic value of some trait of an individual genotype in a population as a function of an environmental parameter. NoRs thus depict the phenotypic plasticity of a trait. The topological properties of NoRs for sets of different genotypes can be used to infer the presence of (non-linear) genotype-environment interactions. While it is clear that many NoRs are adaptive, it is not yet settled whether their evolutionary (...) etiology should be explained by selection on the mean phenotypic trait values in different environments or whether there are specific genes conferring plasticity. If the second alternative is true the NoR is itself an object of selection. Generalized NoRs depict plasticity at the level of populations or subspecies within a species, species within a genus, or taxa at higher levels. Historically, generalized NoRs have routinely been drawn though rarely explicitly recognized as such. Such generalized NoRs can be used to make evolutionary inferences at higher taxonomic levels in a way analagous to how standard NoRs are used for microevolutionary inferences. (shrink)

Traditional, quantitative behavioral geneticists and developmental psychobiologists such as Gilbert Gottlieb have long debated what it would take to create a truly developmental behavioral genetics. These disputes have proven so intractable that disputants have repeatedly suggested that the problem rests on their opponents' conceptual confusion; whilst others have argued that the intractability results from the non-scientific, political motivations of their opponents. The authors provide a different explanation of the intractability of these debates. They show that the disputants have competing interpretations (...) of the concepts of reaction norm, genotype-environment interaction, and gene. The common thread that underlies each of these disagreements, the authors argue, is the relevance of potential variation that is not manifest in any actual population to the understanding of development. (shrink)

Four questions are raised about Mealey's genetic argument: (1) Where is the evidence that secondary sociopathy is less heritable than primary sociopathy? (2) What is the genetic correlation between the two types of sociopathy? (3) How does genotype-environment interaction relate? (4) How strong are the links between our evolutionary past and current heritability?

In recent years, philosophers of science have found a renewed interest in mechanisms. The motivation is the thought that the elucidation of a mechanism generates a causal explanation for the phenomenon under investigation. For example, a question such as, How do rats form spatial memories of their environments?, is answered by elucidating the regular causal mechanisms responsible for the individual development of spatial memory in rats. But consider a slightly different question: How do some rats come to have better spatial (...) memory than other rats? This is a question about the causes of variation responsible for variation in spatial memory. The first question demands an answer about regularity; the second question demands an answer about variation. The account of causal-mechanical explanation on offer by philosophers of science captures regularity, but it neglects variation. In this essay, I attempt to modify the mechanical program so as to incorporate both regularity and variation. The task is to explicate the relationship between the regular causal mechanisms responsible for individual development and the causes of variation responsible for variation in populations. As it turns out, this is precisely the relationship that has divided the biometric research tradition and the developmental research tradition in the long-standing debates over genotype-environment interaction, or G×E. Ultimately, the product will be an account of causal-mechanical explanation that captures both regularity and variation, and which may be utilized to resolve an aspect of the debates over G×E. (shrink)

When Genotype × Environment (G × E) interactions are present, heritability estimates are not interpretable. Mealey cites abundant evidence for G × E interactions in the etiology of sociopathy, thereby completely undermining estimates of the heritability of sociopathy which form the foundation of her model. Without proper evidence for a genetic basis of sociopathy, Mealey's sociobiological model collapses under its own great weight.

How micro- and macroevolutionary evolutionary processes produce phenotypic change is without question one of the most intriguing and perplexing issues facing evolutionary biologists. We believe that roadblocks to progress lie A) in the underestimation of the role of the environment, and in particular, that of the interaction of genotypes with environmental factors, and B) in the continuing lack of incorporation of development into the evolutionary synthesis. We propose the integration of genetic, environmental and developmental perspectives on the evolution (...) of the phenotype in the form of the concept of the developmental reaction norm (DRN) The DRN represents the set of multivariate ontogenies that can be produced by a single genotype when it is exposed to environmental variation. It encompasses: 1) the processes that alter the phenotype throughout the ontogenetic trajectory, 2) the recognition that different aspects of the phenotype are (and must be) correlated and 3) the ability of a genotype to produce phenotypes in different environments. This perspective necessitates the explicit study of character expression during development, the evaluation of associations between pairs or groups of characters (e.g., multivariate allometries), and the exploration of reaction norms and phenotypic plasticity. We explicitly extend the concept of the DRN to encompass adjustments made in response to changes in the internal environment as well. Thus, ‘typical’ developmental sequences (e.g., cell fate determination) and plastic responses are simply manifestations of different scales of ‘environmental’ effects along a continuum. We present: (1) a brief conceptual review of three fundamental aspects of the generation and evolution of phenotypes: the changes in the trajectories describing growth and differentiation (ontogeny), the multivariate relationships among characters (allometry), and the effect of the environment (plasticity); (2) a discussion of how these components are merged in the concept of the developmental reaction norm; and (3) a reaction norm perspective of major determinants of phenotypes: epigenesis, selection and constraint. (shrink)

In her recent article, Prince has identified a critical challenge for those who advocate genetic enhancement to reduce social injustices. The gene–environment interaction prevents genetic enhancement from having equitable effects at the phenotypic level, even if enhancement were available to the entire population. The poor would benefit less than the rich from their improved genes because their genotypes would interact with more unfavourable socioeconomic environments. Therefore, Prince believes that genetic enhancement should not be used to combat social inequalities, (...) since it can likely aggravate them. In this article, I raise various objections to this conclusion. I argue first that genetic enhancement need not necessarily magnify social injustices. I then show that genetic enhancement can play a modest but not insignificant role in the quest for social justice in the future. Finally, I conclude by arguing for the need to consider the complex interplay between the social lottery and the natural lottery in our aspirations for justice linked to genetic technologies. (shrink)

Males are selectively afflicted with the neurodevelopmental and psychiatric disorders of childhood, a broad and virtually ubiquitous phenomenon that has not received proper attention in the biological study of sex differences. The previous literature has alluded to psychosocial differences, genetic factors and elements pertaining to male “complexity” and relative immaturity, but these are not deemed an adequate explanation for selective male affliction. The structure of sex differences in neurodevelopmental disorders is hypothesized to contain these elements: Males are more frequently afflicted, (...) females more severely; disorders arising in females are largely mediated by the genotype; in males, by a genotype by environment interaction; complications of pregnancy and delivery occur more frequently with male births; such complications are decisive and influence subsequent development. We hypothesize that there is something about the male fetus that evokes an inhospitable uterine environment. This “evocative principle” is hypothesized to relate to the relative antigenicity of the male fetus, which may induce a state of maternal immunoreactivity, leading either directly or indirectly to fetal damage. The immunoreactive theory thus constructed is borrowed from studies of sex ratios and is the only explanation consistent with negative parity effects in the occurrence of pregnancy complications and certain neurodevelopmental disorders. Although the theory is necessarily speculative, it is heuristic and hypotheses derived from it are proposed; some are confirmed in the existing literature and by the authors' research. (shrink)

Dewi et Eka sont de vraies jumelles nées dans la province sud du Kalimantan, à Bornéo. La première est sauvée d’un effroyable incendie dans lequel tout le monde pense qu’a péri Eka. En fait, cette dernière a été récupérée par une femelle orang-outan qui l’élèvera. Dewi, elle, sera l’une des femmes les plus brillantes de sa génération, et recevra le prix Nobel de physiologie et médecine. Eka, quant à elle, bien que recueillie dans une société humaine à dix ans, restera (...) une enfant sauvage souffrant d’un grave retard mental. Elle mourra misérablement. Les deux soeurs ont pourtant les mêmes gènes. Comment Dewi a-t-elle pu développer les outils d’un brillant épanouissement pleinement humain, quelles en furent les étapes et les conditions? Pourquoi tout cela n’a-t-il pu s’enclencher chez Eka? Axel Kahn utilise la fiction pour introduire la thématique qu’il développe à travers un essai, s’attachant à enrichir, touche après touche, l’observation de ses héroïnes gémellaires dont l’image et l’exemple traversent l’ouvrage. Il rappelle le rôle de l’altérité de l’un et l’autre, comme deux bûches incandescentes qui s’embrasent l’une l’autre, et nous enjoint : «Osons vouloir, alors nous pourrons, peut-être.». (shrink)

Obesity and type 2 diabetes arise from a set of complex gene–environment interactions. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the “thrifty genotype” and the “thrifty phenotype” hypotheses. Here, the merits of both models are discussed and elements of them are used to synthesize a “thrifty epigenotype” hypothesis. I propose that: (1) metabolic thrift, the capacity for efficient acquisition, storage and use of energy, is an ancient, complex trait, (...) (2) the environmentally responsive gene network encoding this trait is subject to genetic canalization and thereby has become robust against mutational perturbations, (3) DNA sequence polymorphisms play a minor role in the aetiology of obesity and type 2 diabetes—instead, disease susceptibility is predominantly determined by epigenetic variations, (4) corresponding epigenotypes have the potential to be inherited across generations, and (5) Leptin is a candidate gene for the acquisition of a thrifty epigenotype. BioEssays 30:156–166, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Ernst Mayr proposed a distinction between “proximate”, mechanistic, and “ultimate”, evolutionary, causes of biological phenomena. This dichotomy has influenced the thinking of many biologists, but it is increasingly perceived as impeding modern studies of evolutionary processes, including study of “niche construction” in which organisms alter their environments in ways supportive of their evolutionary success. Some still find value for this dichotomy in its separation of answers to “how?” versus “why?”questions about evolution. But “why is A?” questions about evolution necessarily take (...) the form “how does A occur?”, so this separation is illusory. Moreover, the dichotomy distorts our view of evolutionary causality, in that, contra Mayr, the action of natural selection, driven by genotype-phenotype-environment interactions which constitute adaptations, is no less “proximate” than the biological mechanisms which are altered by naturally selected genetic variants. Mayr’s dichotomy thus needs replacement by more realistic, mechanistic views of evolution. From a mechanistic viewpoint, there is a continuum of adaptations from those evolving as responses to unchanging environmental pressures to those evolving as the capacity for niche construction, and intermediate stages of this can be identified. Some biologists postulate an association of “phenotypic plasticity” (phenotype-environment covariation with genotype held constant) with capacity for niche construction. Both “plasticity” and niche construction comprise wide ranges of adaptive mechanisms, often fully heritable and resulting from case-specific evolution. Association of “plasticity” with niche construction is most likely to arise in systems wherein capacity for complex learning and behavioral flexibility have already evolved. (shrink)

Major contributions emanating from Sagvolden et al.'s theory include elucidation of the role in attention-deficit/hyperactivity disorder (ADHD) of temporal information processing, social learning, and response extinction learning. Key issues include a need for clearer explanation of the relative role of impulsivity versus response suppression/inhibition in the dual process model, and delineation of genotype-environment correlations versus interactions in the social and experiential mechanisms posited.

Ethical debates around genetic enhancement tend to include an argument that the technology will eventually be fairly accessible once available. That we can fairly distribute genetic enhancement has become a moral defence of genetic enhancement. Two distribution solutions are argued for, the first being equal distribution. Equality of access is generally believed to be the fairest and most just method of distribution. Second, equitable distribution: providing genetic enhancements to reduce social inequalities. In this paper, I make two claims. I first (...) argue that the very assumption that genetic enhancements can be distributed fairly is problematic when considering our understanding of gene–environment interactions, for example, epigenetics. I then argue that arguments that genetic enhancements are permissible because the intended benefits can be distributed fairly as intended are misinformed. My first claim rests on the assertion that genetic enhancements do not enhance traits in a vacuum; genes are dependent on conducive environments for expression. If society cannot guarantee fair environments, then any benefit conferred from being genetically enhanced will be undermined. Thus, any argument that the distribution of genetic enhancements will be fair and that the technology is therefore morally permissible, is mistaken. (shrink)

This article presents a holistic framework for understanding the scienceof plant breeding, as an alternative to the common objectivist andconstructivist approaches in studies of science. It applies thisapproach to understanding disagreements about how to deal with yieldstability. Two contrasting definitions of yield stability are described,and concomitant differences in the understanding and roles ofsustainability and of selection, test, and target environments areexplored. Critical questions about plant breeding theory and practiceare posed, and answers from the viewpoint of the two contrastingdefinitions of yield (...) stability are analyzed, based on key publicationsin the field. Differences in answers to these questions appear to resultboth from the contingencies of plant breeders' experiences withparticular crop varieties and growing environments, and from differencesin social and institutional settings – plant breeding science isboth objective truth and social construction. The goal of using aholistic framework is to encourage discussion among plant breeders,farmers, social scientists, and others, of the bases for disagreementswithin plant breeding, in order to facilitate plant breeding'scontribution to a more environmentally, economically, and sociallysustainable agriculture. (shrink)

Although the field of psychiatry has witnessed the proliferation of studies on Gene x Environment (GxE) interactions, still limited is the knowledge we possess of GxE interactions regarding developmental disorders. In this perspective paper, we discuss why GxE interaction studies are needed to broaden our knowledge of developmental disorders. We also discuss the different roles of hazardous versus self-generated environmental factors and how these types of factors may differentially engage with an individual’s genetic background in predicting a resulting (...) phenotype. Then, we present exemplar studies that highlight the role of GxE in predicting atypical developmental trajectories as well as provide insight regarding treatment outcomes. Supported by these examples, we explicate the need to move beyond merely examining statistical interactions between genes and the environment, and to investigate specific genetic susceptibility and environmental contexts that drive developmental disorders. We propose that further parsing of genetic and environmental components is required to fully understand the unique contribution of each factor to the etiology of developmental disorders. Finally, with a greater appreciation of the complexities of GxE interaction, this discussion will converge upon the potential implications for clinical and translational research. (shrink)

I argue that a phenotypic trait can be an adaptation to a particular environmental condition, as against others, only if the environmental condition and the phenotype interactively cause fitness. Models of interactive environmental causes of fitness generally require that environments be individuated by explicit representation rather than by measures of environmental quality, although the latter understanding of ‘environment’ is more prominent in the philosophy of biology. Hence, talk of adaptations to some but not other environmental conditions relies on conceptions (...) of ‘environment’ importantly different from that commonly presupposed in philosophy of biology. (shrink)

The idea of organism-environment interaction, at least in its modern form, dates only to the mid-nineteenth century. After sketching the origins of the organism-environment dichotomy in the work of Auguste Comte and Herbert Spencer, I will chart its metaphysical and methodological influence on later scientists and philosophers such as Conwy Lloyd Morgan and John Dewey. In biology and psychology, the environment was seen as a causal agent, highlighting questions of organismic variation and plasticity. In philosophy, organism- (...) class='Hi'>environment interaction provided a new foundation for ethics, politics, and scientific inquiry. Thinking about organism-environment interaction became indispensable, for it had restructured our view of the biological and social world. (shrink)

The idea of representation is central to many theories for embodied skillful action. Representation-centric cognition has been questioned in light of the prominence of E-cognition in the past two decades, including ecological psychology, sensorimotor theory, dynamical systems, and 4E cognition. The paper expands on the critique by offering alternate explanations for the information processing model of skill learning and embodied action. Mental representation plays a fundamental role in information processing explanations of embodied skillful action. The skilled activity is considered discretely (...) in information-theoretic approaches, consisting of a linear model of information input-process-output. According to the paper, the beginning, emergence, acquisition, performance, and mastery of an embodied skilled activity are all part of a human experience continuum. Using vehicle driving as an example, the paper examines diverse viewpoints on embodied skillful action. (shrink)

I provide a history of research on G×E in this article, showing that there have actually been two distinct concepts of G×E since the very origins of this research. R. A. Fisher introduced what I call the biometric concept of G×E, or G×EB, while Lancelot Hogben introduced what I call the developmental concept of G×E, or G×ED. Much of the subsequent history of research on G×E has largely consisted in the separate legacies of these separate concepts, along with the (sometimes (...) acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, I then consider more recent attempts to distinguish between different concepts of G×E, paying particular attention to the commonly made distinction between “statistical interaction” and “interactionism,” and also Michael Rutter’s distinction between “statistical interaction” and “the biological concept of interaction.” I argue that the history of the separate legacies of G×EB and G×ED better supports Rutter’s analysis of the situation, and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G×E in the etiology of complex traits. (shrink)

Scientists now agree that common diseases arise through interactions of genetic and environmental factors, but there is less agreement about how scientific research should account for these interactions. This paper examines the politics of quantification in gene–environment interaction research. Drawing on interviews and observations with GEI researchers who study common, complex diseases, we describe quantification as an unfolding moral economy of science, in which researchers collectively enact competing “virtues.” Dominant virtues include molecular precision, in which behavioral and social (...) risk factors are moved into the body, and “harmonization,” in which scientists create large data sets and common interests in multisited consortia. We describe the negotiations and trade-offs scientists enact in order to produce credible knowledge and the forms of discipline that shape researchers, their practices, and objects of study. We describe how prevailing techniques of quantification are premised on the shrinking of the environment in the interest of producing harmonized data and harmonious scientists, leading some scientists to argue that social, economic, and political influences on disease patterns are sidelined in postgenomic research. We consider how a variety of GEI researchers navigate quantification’s productive and limiting effects on the science of etiological complexity. (shrink)

This dissertation concerns the active role of the organism in evolutionary theory. In particular, it concerns how our conception of the relationship between organism and environment, and the nature of natural selection, influences the causal and explanatory role of organismic activity and behavior in evolutionary explanations. The overarching aim is to argue that the behaviors and activities of organisms can serve both as the explananda (that which is explained) and the explanantia (that which explains) in evolutionary explanations. I attempt (...) to achieve this aim by offering three central arguments. First, that the organism-environment relation is the ontologically basic unit of biology. A common way of conceiving the relationship between organism and environment is as a duality—as two causally independent systems that overlap through interaction. I think this is a mistake. There cannot be organisms without environments and vice versa. They are codependent and codetermined. Second, that natural selection is an ecological process. By this I mean that natural selection acts primarily on organism-environment interactions. It is only in virtue of organisms interacting with their environments that there can be fitness differences amongst individual organisms in a population. The ecological approach to natural selection also entails that the nature of the system(s) of inheritance involved in the reoccurrence of favorable organism-environment interactions is, in principle, immaterial to the process of selection. It only matters for selection that organism-environment interactions actually do reoccur in subsequent generations. Third, that niche construction theory—the most well-developed theoretical and conceptual framework for studying how the activities of organisms influences evolutionary dynamics—can be seen as fully a compatible and integrated part of evolutionary theory. Together, these three arguments constitute an overarching argument. Namely that we both can, and should, take organismic activity and behavior to be crucial explanatory elements in evolutionary theory. Throughout the dissertation I also show how these three arguments have consequences for other debates in the philosophy of evolutionary theory, such as the nature of evolutionary processes, the structure of selection-based explanations, the validity and utility of the proximate-ultimate distinction, and the nature of teleology in evolutionary systems. (shrink)

Two prevailing paradigms explain the diversity of sex-determining modes in reptiles. Many researchers, particularly those who study reptiles, consider genetic and environmental sex-determining mechanisms to be fundamentally different, and that one can be demonstrated experimentally to the exclusion of the other. Other researchers, principally those who take a broader taxonomic perspective, argue that no clear boundaries exist between them. Indeed, we argue that genetic and environmental sex determination in reptiles should be seen as a continuum of states represented by species (...) whose sex is determined primarily by genotype, species where genetic and environmental mechanisms coexist and interact in lesser or greater measure to bring about sex phenotypes, and species where sex is determined primarily by environment. To do otherwise limits the scope of investigations into the transition between the two and reduces opportunities to use studies of reptiles to advance understanding of vertebrate sex determination generally. © 2004 Wiley Periodicals, Inc. (shrink)

The presence of gene–environment statistical interaction and correlation in biological development has led both practitioners and philosophers of science to question the legitimacy of heritability estimates. The paper offers a novel approach to assess the impact of GxE and rGE on the way genetic and environmental causation can be partitioned. A probabilistic framework is developed, based on a quantitative genetic model that incorporates GxE and rGE, offering a rigorous way of interpreting heritability estimates. Specifically, given an estimate of (...) heritability and the variance components associated with estimates of GxE and rGE, I arrive at a probabilistic account of the relative effect of genes and environment. (shrink)

The environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. It is conjectured that such complex systems cannot interact directly, but rather their interaction requires the formation of an intermediary “interface.” This position contrasts with current epidemiological constructs of causation, which implicitly assume that two complex systems transfer information directly while remaining separate entities. Further, it is contended that dynamic, process‐based interfaces incorporate components from (...) all the interacting systems but exhibit operational independence. This property has many consequences, the foremost being that characteristics of the interface cannot be fully resolved by only studying the systems involved in the interaction. The interface itself must be the subject of inquiry. Without refocusing the attention on biodynamic interfaces, how the environment impacts health cannot be discerned. Also see the video abstract here https://youtu.be/XeyjeZeyo4o. (shrink)

The word ‘environment’ has a history. Before the mid-nineteenth century, the idea of a singular, abstract entity—the organism—interacting with another singular, abstract entity—the environment—was virtually unknown. In this paper I trace how the idea of a plurality of external conditions or circumstances was replaced by the idea of a singular environment. The central figure behind this shift, at least in Anglo-American intellectual life, was the philosopher Herbert Spencer. I examine Spencer’s work from 1840 to 1855, demonstrating that (...) he was exposed to a variety of discussions of the ‘force of circumstances’ in this period, and was decisively influenced by the ideas of Auguste Comte in the years preceding the publication of Principles of psychology (1855). It is this latter work that popularized the word ‘environment’ and the corresponding idea of organism–environment interaction—an idea with important metaphysical and methodological implications. Spencer introduced into the English-speaking world one of our most enduring dichotomies: organism and environment. (shrink)

In our commentary we ask whether we should ultimately endeavour to find the deep causes of behaviours? Then we discuss two extensions of the proposed framework: (1) Mendelian randomisation and (2) hypothesis-free gene–environment interaction (leveraging heterogeneity in genetic associations). These complementary methods help move us towards second-generation causal knowledge, ultimately understanding mechanistic pathways and identifying more effective intervention targets.

The following three points are made. One must consider not only the levels of circulating hormone but the target tissue upon which the hormone acts. Increased testosterone levels alone do not account for differences in displayed intermale aggression, because testosterone and social environment interact in complex ways to influence behavior. A given behavior can be triggered by multiple motivational systems.

In a widely acclaimed study from 2002, researchers found a case of gene-environment interaction for a gene controlling neuroenzymatic activity (low vs. high), exposure to childhood maltreatment, and antisocial personality disorder (ASPD). Cases of gene-environment interaction are generally characterized as evincing a genetic predisposition; for example, individuals with low neuroenzymatic activity are generally characterized as having a genetic predisposition to ASPD. I first argue that the concept of a genetic predisposition fundamentally misconstrues these cases of gene- (...) class='Hi'>environment interaction. This misconstrual will be diagnosed, and then a new concept—interactive predisposition—will be introduced. I then show how this conceptual shift reconfigures old questions and raises new questions for genetic screening. Attempts to screen embryos or fetuses for the gene associated with low neuroenzymatic activity with an eye towards selecting against the low-activity variant fall prey to the myth of pre-environmental prediction; attempts to screen newborns for the gene associated with low neuroenzymatic activity with an eye towards early intervention will have to face the interventionist’s dilemma. (shrink)

Again and again utopian hopes are connected with the life sciences (no hunger, health for everyone; life without diseases, longevity), but simultaneously serious research shows uncertain, incoherent, and ambivalent results. It is unrealistic to expect that these uncertainties will disappear. We start by providing a not exhaustive list of five different types of uncertainties end-users of nutrigenomics have to cope with without being able to perceive them as risks and to subject them to risk-analysis. First, genes connected with the human (...) body or nutrients can have different functions in interaction with their environment (for instance, one nutrient can be healthy for the heart, but can also be a high risk in relation to cancer). Secondly, uncertainties are formed by risk analyses. Will it be possible to calculate a certain risk of getting a certain condition with a certain lifestyle? Will it be difficult to separate the genetic component and the lifestyle component? How high will these risks be? How will these risks be handled by the actors? In the case of personal genotyping, it is unclear how frequent an adverse polymorphism will occur. Will every individual have a certain vulnerability to a certain disease or will it only be applicable to a small group of the population or particular populations? Thirdly, dietary advices are subject to uncertainties and still to be developed professional standards: some will have adverse outcomes, some will not delay the disease, and some will assume uncertain associations between nutrients, lifestyle, and genetic vulnerabilities. Fourth, with regard to the usefulness of tests it is uncertain to what extent risks indications about obesity and diabetes and other vulnerabilities really influence people to live healthier and therefore will help to prevent these conditions. Fifth, it is uncertain how and what nutrigenomics products will be developed and used. Will it be possible to develop more effectively health improving products? Or is this too difficult and will nutrigenomics continue to be used in not always justified health claims as a commercial and marketing tool? Present-day ethics and theories of responsibilities presuppose that uncertainties will disappear and concentrate on what seems to be fixed and stable in science. We develop provisional thoughts that assume that the dynamic of science to produce uncertainties and dilemmas is endemic, and we stress the need for consumers to institutionalize value searching, exploring, and deliberating devices in the health and food sector to find out the most important uncertainties and correspondingly socially desirable research priorities. (shrink)

Polygenic score (PGS) computations assume an additive model of gene action because associations between phenotypes and alleles at different loci are compounded, ignoring interactions between alleles or loci let alone between genotype and environment. Consequently, PGSs are subject to the same objections that invalidated traditional heritability analyses in the 1970s. Thus, PGSs should not be used in the social sciences.