title: Interactive effects of in utero nutrition and genetic inheritance on cognition: new evidence using sibling comparisons.
abstract: A large literature links early environments and later outcomes, such as cognition; however, little is known about the mechanisms. One potential mechanism is sensitivity to early environments that is moderated or amplified by the genotype. With this mechanism in mind, a complementary literature outside economics examines the interaction between genes and environments, but often problems of endogeneity and bias in estimation are uncorrected. A key issue in the literature is exploring environmental variation that is not exogenous, which is potentially problematic if there are gene-environment correlation or gene-gene interactions. Using sibling pairs with genetic data in the Wisconsin Longitudinal Study we extend a previous, and widely cited, gene-environment study that explores an interaction between the FADS2 gene, which is associated with the processing of essential fatty acids related to cognitive development, and early life nutrition in explaining later-life IQ. Our base OLS findings suggest that individuals with specific FADS2 variants gain roughly 0.15 standard deviations in IQ for each standard deviation increase in birth weight, our measure of the early nutrition environment; while, individuals with other variants of FADS2 do not have a statistically significant association with early nutrition, implying the genotype is influencing the effects of environmental exposure. When including family-level fixed effects, however, the magnitude of the gene-environment interaction is reduced by half and statistical significance dissipates, implying the interaction between FADS2 and early nutrition in explaining later life IQ may in part be due to unobserved, family-level factors. The example has wider implications for the practice of investigating gene-environment interactions when the environmental exposure is not exogenous and robustness to unobserved variation in the genome is not controlled for in the analysis.
authors.affiliation: University of Wisconsin-Madison, United States.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Cook
authors.affiliation: University of Wisconsin-Madison, United States. Electronic address: jmfletcher@wisc.edu.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Fletcher
mesh_terms: D001724:Birth Weight; D003071:Cognition; D004777:Environment; D044943:Fatty Acid Desaturases; D059647:Gene-Environment Interaction; D005838:Genotype; D006803:Human Development; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008137:Longitudinal Studies; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D035781:Siblings
chemical_list: D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: Gene–environment interaction; IQ; Nutrition; Sibling fixed effects