Disentangling the Contribution of Childhood and Adulthood Circumstances and Genetics to Phenotypic Aging

Zuyun Liu , Yale University
Xi Chen, Yale University
Thomas Gill, Yale University
Chao Ma, Yale University
Eileen Crimmins, University of Southern California
Morgan Levine, Yale University

To evaluate the extent to which childhood and adulthood circumstances and genetics contribute to phenotypic aging, we included 2,339 adults (aged 51+ years) from U.S. Health and Retirement Study and calculated their Phenotypic Age acceleration (PhenoAgeAccel), which represents phenotypic aging after accounting for chronological age. The Shapley Value Decomposition approach revealed that together all 11 studied domains accounted for about 30% of variance in PhenoAgeAccel. Among them, the polygenic scores contributed 3.8% of variance in PhenoAgeAccel. Further, six subpopulations/clusters—identified based on childhood and adulthood SES and adversity—showed different PhenoAgeAccel. Finally, there was a significant gene-by-environment interaction between a previously validated PGS for coronary artery disease (CAD) and the most apparently disadvantaged subpopulation/cluster. In summary, socioenvironmental circumstances during childhood and adulthood account for a sizable proportion of differences in phenotypic aging among U.S. older adults. The detrimental effects may be further exacerbated among persons with genetic predisposition to CAD.

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 Presented in Session 232. Gene-Environment Interaction and Health