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Misclassification of heritable mortality undermines estimates of intrinsic life span heritability

Hamilton, F. W.

2026-02-27 genetic and genomic medicine
10.64898/2026.02.26.26347172 medRxiv
Show abstract

In a recent article in Science, Shenhar et al. report that human life span heritability reaches [~]55% after removing "extrinsic" mortality, roughly seven-fold higher than recent large pedigree estimates. This conclusion rests on classifying deaths from infections and accidents as environmental noise independent of genetics. This premise is biologically untenable: susceptibility to severe infection is substantially heritable, with adoptee studies showing relative risks exceeding 5 for infection death when a biological parent died of infection. By encoding the assumption that extrinsic mortality is non-genetic directly into their Gompertz-Makeham model, removing it necessarily inflates heritability estimates. This creates selection bias rather than correcting for confounding and explains the contradiction with both pedigree studies and GWAS findings. The proposed heritability estimate is therefore not the true heritability of any population, past or present.

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