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Heritability of human lifespan is about 50% when confounding factors are addressed

Shenhar, B.; Pridham, G.; de Oliveira, T. L.; Yang, Y.; Raz, N.; Deelen, J.; Hagg, S.; Alon, U.

2025-04-21 genetics
10.1101/2025.04.20.649385 bioRxiv
Show abstract

The heritability of human lifespan is a fundamental question in biology. Current estimates of heritability are low - twin studies show that about 20-25% of the variation in lifespan is explained by genetics, and some large family pedigree studies suggest it is as low as 7%. However, these studies do not distinguish between deaths driven by intrinsic biological processes and deaths caused by extrinsic factors such as accidents or infections. Here we use mathematical modeling and analyses of twin cohorts raised together and apart to show that extrinsic mortality skews heritability estimates by driving down measured lifespan correlations among twin pairs. We also identify a nonlinear effect of the cutoff age--the minimum age of death included in each study -- on estimates of heritability. Correcting for these factors more than doubles previous estimates, revealing that intrinsic heritability of human lifespan is above 50%. Such high heritability is similar to most other complex human traits. We thus challenge the consensus that genetics has only a minor effect on lifespan and show that genes explain the majority of lifespan variation. Since genes are important, understanding the genetics of longevity can reveal aging mechanisms and inform medicine and public health.

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