title: Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures.
abstract: Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA. bmdonofr@indiana.edu.
authors.forename: Brian M
authors.identifier: 0000-0002-5248-7434
authors.initials: BM
authors.lastname: D'Onofrio
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA.
authors.forename: Quetzal A
authors.initials: QA
authors.lastname: Class
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Rickert
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA.
authors.forename: Ayesha C
authors.initials: AC
authors.lastname: Sujan
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Larsson
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kuja-Halkola
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arvid
authors.initials: A
authors.lastname: Sjölander
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Catarina
authors.initials: C
authors.lastname: Almqvist
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.|Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: A Sara
authors.initials: AS
authors.lastname: Oberg
mesh_terms: D015986:Confounding Factors, Epidemiologic; D005190:Family; D005260:Female; D006801:Humans; D008957:Models, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D057170:Translational Research, Biomedical
keywords: Causal inference; Cousin comparisons; Developmental origins of health and disease; Fetal growth; Genetically-informed designs; Pregnancy; Sibling comparisons