Behavior Genetics

, Volume 46, Issue 3, pp 315–328 | Cite as

Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures

  • Brian M. D’OnofrioEmail author
  • Quetzal A. Class
  • Martin E. Rickert
  • Ayesha C. Sujan
  • Henrik Larsson
  • Ralf Kuja-Halkola
  • Arvid Sjölander
  • Catarina Almqvist
  • Paul Lichtenstein
  • A. Sara Oberg


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.


Causal inference Genetically-informed designs Sibling comparisons Cousin comparisons Developmental origins of health and disease Pregnancy Fetal growth 



We acknowledge financial support from the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM, Grant No. 340-2013-5867), NICHD (HD061817 and HD061384), and NIMH (MH094011 and MH102221).


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Brian M. D’Onofrio
    • 1
    Email author return OK on get
  • Quetzal A. Class
    • 1
  • Martin E. Rickert
    • 1
  • Ayesha C. Sujan
    • 1
  • Henrik Larsson
    • 2
  • Ralf Kuja-Halkola
    • 2
  • Arvid Sjölander
    • 2
  • Catarina Almqvist
    • 2
  • Paul Lichtenstein
    • 2
  • A. Sara Oberg
    • 2
    • 3
  1. 1.Department of Psychological and Brain SciencesIndiana UniversityBloomingtonUSA
  2. 2.Karolinska InstitutetStockholmSweden
  3. 3.Harvard T.H. Chan School of Public HealthBostonUSA

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