Separating Scarring Effect and Selection of Early-Life Exposures With Genetic Data

Author:

Furuya Shiro1ORCID,Zheng Fengyi2ORCID,Lu Qiongshi3ORCID,Fletcher Jason M.4ORCID

Affiliation:

1. Department of Sociology, Center for Demography of Health and Aging, and Center for Demography and Ecology, University of Wisconsin–Madison, Madison, WI, USA

2. Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA

3. Center for Demography of Health and Aging, Department of Statistics, and Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison, WI, USA

4. Center for Demography of Health and Aging, Center for Demography and Ecology, La Follette School of Public Affairs, Department of Population Health Science, and Department of Agricultural and Applied Economics, University of Wisconsin–Madison, Madison, WI, USA

Abstract

Abstract Causal life course research examining consequences of early-life exposures has largely relied on associations between early-life environments and later-life outcomes using exogenous environmental shocks. Nonetheless, even with (quasi-)randomized early-life exposures, these associations may reflect not only causation (“scarring”) but also selection (i.e., which members are included in data assessing later life). Investigating this selection and its impacts on estimated effects of early-life conditions has, however, often been ignored because of a lack of pre-exposure data. This study proposes an approach for assessing and correcting selection, separately from scarring, using genetic measurements. Because genetic measurements are determined at the time of conception, any associations with early-life exposures should be interpreted as selection. Using data from the UK Biobank, we find that in utero exposure to a higher area-level infant mortality rate is associated with genetic predispositions correlated with better educational attainment and health. These findings point to the direction and magnitude of selection from this exposure. Corrections for this selection in examinations of effects of exposure on later educational attainment suggest underestimates of 26–74%; effects on other life course outcomes also vary across selection correction methods.

Publisher

Duke University Press

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