An Exploration of Gene–Environment Interaction and Asthma in a Large Sample of 5-Year-Old Dutch Twins

Abstract

A consistent finding from twin studies is that the environment shared by family members does not contribute to the variation in susceptibility to asthma. At the same time, it is known that environmental risk factors that are shared by family members are associated with the liability for asthma. We hypothesize that the absence of a main effect of shared environmental factors in twin studies can be explained by gene–environment interaction, that is, that the effect of an environmental factor shared by family members depends on the genotype of the individual. We explore this hypothesis by modeling the resemblance in asthma liability in twin pairs as a function of various environmental risk factors and test for gene–environment interaction. Asthma data were obtained by parental report for nearly 12,000 5-year-old twin pairs. A series of environmental risk factors was examined: birth cohort, gestational age, time spent in incubator, breastfeeding, maternal educational level, maternal smoking during pregnancy, current smoking of parents, having older siblings, and amount of child care outside home. Results revealed that being a boy, born in the 1990s, premature birth, longer incubator time, and child care outside home increased the risk for asthma. With the exception of premature birth, however, none of these factors modified the genetic effects on asthma. In very premature children shared environmental influences were important. In children born after a gestation of 32 weeks or more only genetic factors were important to explain familial resemblance for asthma.

A Twin Study of Early-Childhood Asthma in Puerto Ricans

“…Recent twin studies of asthma argue that genetic factors primarily explain asthma susceptibility,[5]–[7] and that shared environmental factors do not contribute to its variation [8]. In this study, we assess the relative contributions of genetics and environment to asthma susceptibility and its variation with age by conducting a longitudinal twin study of asthma starting in infancy.…”

Operating Characteristics of Alternative Statistical Methods for Detecting Gene-by-Measured Environment Interaction in the Presence of Gene–Environment Correlation in Twin and Sibling Studies

“…There, he proposed an important extension of the classic bivariate biometric model to allow testing interactions between a measured environment and each of the variance components (A, C, or E), while accounting for A-, C-, or E-by-measured environment correlations arising from the influence of genes (A) and environmental factors (C and E) common to both the phenotype and the measured environment. Since the publication of Purcell’s article, researchers have relied on his model to test gene-by-environment interactions for a wide range of phenotypes, including perceived control and physical health (Johnson & Krueger, 2005), family income and intelligence scores (Turkheimer, Haley, Waldron, D’Onofrio, & Gottesman, 2003), prenatal complications and asthma (van Beijsterveldt & Boomsma, 2008), protein intake and body composition (Silventoinen et al, 2009), marital quality and anxiety (South & Krueger, 2008), and others (Johnson, McCue, & Iacono, 2009; Lau & Eley, 2008). Whereas interactions between candidate moderators and additive genetic influences (A) were usually the focus of these studies, researchers typically tested the potentially important interactions between the candidate moderator and shared (C) and unshared (E) environmental influences as well.…”

Gene–environment interaction in atopic diseases: a population‐based twin study of early‐life exposures

“…Van Beijsterveldt et al . are among the few who have examined genetic effect modification in relation to atopic diseases in a twin study . They found that the relative genetic contribution to the susceptibility to asthma in Dutch twins decreased significantly from 90% in children born at term to 45% in children born at a gestational age of less than 32 weeks, and that the relative contribution of shared environment increased from 0% to 52%.…”