Twins and Causal Inference: Leveraging Nature's Experiment

Abstract

In this paper we discuss how samples comprising monozygotic and dizygotic twin pairs can be used for the purpose of strengthening causal inference by controlling for shared influences on exposure and outcome. We begin by briefly introducing how twin data can be used to inform the biometric decomposition of population variance into genetic, shared-environmental and non-shared environmental influences. We then discuss how extensions to this model can be used to explore whether associations between exposure and outcome survive correction for shared aetiology (common causes). We review several analytical approaches that can be applied to twin data for this purpose. These include multivariate structural equation models, co-twin control methods, direction of causation models (cross-sectional and longitudinal), and extended family designs used to assess intergenerational associations. We conclude by highlighting some of the limitations and considerations that researchers should be aware of when using twin data for the purposes of interrogating causal hypotheses.

Systematic Review and Meta-analysis of Genetically Informed Research: Associations Between Parent Anxiety and Offspring Internalizing Problems

“…51,59 It is also possible for both children-of-twins and sibling-comparison designs to overcorrect for genetic relatedness if genetic factors comprise an integral part of the causal pathway in parent-tochild environmental transmission, rather than acting as confounders across generations. 85 Further, in both designs, it is possible for the effects of evocative gene-environment correlation to inflate estimates of the parent's causal influence on the child.…”

Causal Inference with Genetic Data: Past, Present, and Future

“…The rest of this collection focuses more pragmatically on describing genetically informed methods for causal inference and their applications. Thapar and Rice (2021) present a range of family-based designs for causal inference while McAdams et al (2021) focus on the twin design and its extensions to larger pedigrees. Richmond and Davey Smith (2021) turn to explaining the fundamentals of MR and how genetic variants and in particular SNPs can be used as instruments for causal inference.…”

The Meaning of “Cause” in Genetics

“…This premise has been contested by some (Kendler et al 1993;Horwitz et al 2003), although supported by others, for instance by studying twin pairs with mistaken zygosity (Scarr and Carter-Saltzman 1979;Borkenau et al 2002). More details of familybased designs can be found in Thapar and Rice (2021), McAdams et al (2021), andHwang et al (2021).…”

“…Correlations between particular genotypes and environments (rGEs) can occur when an individual's genotype causally influences the environment in which they develop, or when there is a common cause of an individual's genotype and of their environment. rGEs are commonly divided into three different types: active, evocative (also called reactive), and passive (Plomin et al 1977;Scarr and McCartney 1983) and are further addressed in McAdams et al (2021) and Thapar and Rice (2021).…”