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bioRxiv · 10.1101/384040

Disentangling the contribution of childhood and adulthood circumstances and genetics to phenotypic aging: prospective cohort study

Liu, Z.·Chen, X.·Gill, T. M.·Ma, C.·Crimmins, E. M.·Levine, M. E.
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Abstract

ObjectivesTo evaluate the extent to which childhood and adulthood circumstances and genetics contribute to phenotypic aging, using a multi-system-based signature of aging that has been shown to capture mortality and morbidity risk.\n\nDesignProspective population-based cohort study.\n\nSettingUnited States (U.S.).\n\nParticipants2,339 adults (aged 51+ years) from U.S. Health and Retirement Study, who participated in the Core Survey, the 2016 Venous Blood Study, the 2015 Life History Mail Survey, the Enhanced Face-To-Face interview (2006-2016), and were part of the genetic sample.\n\nMain outcomes measurePhenotypic Age, a validated aging measure based on a linear combination of chronological age and nine multi-system biomarkers. For most analyses, we examined \"PhenoAgeAccel\", which represents phenotypic aging after accounting for chronological age (i.e. whether a person appears older [positive value] or younger [negative value] than expected, physiologically).\n\nResultsThe Shapley Value Decomposition approach revealed that together all 11 domains (four childhood and adulthood circumstances domains, five polygenic scores [PGSs] domains, demographics, and behaviors domains) accounted for about 30% of variance in PhenoAgeAccel. Among the four circumstances domains, adulthood adversity was the largest contributor (9%), while adulthood socioeconomic status (SES), childhood adversity, and childhood SES accounted for 2.8%, 2.1%, 0.7%, respectively. Collectively, all PGSs contributed 3.8% of variance in PhenoAgeAccel. Further, six subpopulations/clusters--identified using a hierarchical cluster analysis based on childhood and adulthood SES and adversity--showed differences in average levels of phenotypic aging. Finally, there was a significant gene-by-environment interaction between a previously validated PGS for coronary artery disease and the most apparently disadvantaged subpopulation/cluster--suggesting a multiplicative effect of adverse environment coupled with genetic risk on phenotypic aging.\n\nConclusionsSocioenvironmental circumstances during both childhood and adulthood account for a sizable proportion of the difference in phenotypic aging among U.S. older adults. The detrimental effects may further be exacerbated among persons with a genetic predisposition to coronary artery disease.

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Liu, Z., Chen, X., Gill, T. M., Ma, C., Crimmins, E. M., Levine, M. E.. 2018-08-03. Disentangling the contribution of childhood and adulthood circumstances and genetics to phenotypic aging: prospective cohort study. https://doi.org/10.1101/384040

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