Genetic Architecture of Reproduction and Longevity in Historical Dutch Cohorts

Abstract

Life-history theory predicts genetic trade-offs between reproduction and survival, often invoked to explain ageing through antagonistic pleiotropy, but evidence in humans is mixed. We analysed a historical Dutch genealogical dataset (birth cohorts 1850-1915) to estimate pedigree-based heritabilities and genetic correlations among lifespan, offspring number, and ages at first and last birth (AFB and ALB). Bayesian animal models were fitted by sex in samples surviving beyond ages 45 and 13, with year of birth modelled by a natural spline. Lifespan heritability was approximately 0.19-0.23. Reproductive-trait heritabilities varied by sex and were generally higher in men. Cross-sex genetic correlations were substantial. Genetic correlations between offspring number and lifespan were weakly negative in women (-0.10), near zero in men aged 45+, and weakly positive in men aged 13+. AFB was positively genetically correlated with lifespan, especially in the 13+ sample. Offspring number was strongly genetically correlated with earlier AFB and later ALB, while AFB and ALB shared positive genetic covariance. Phenotypic associations changed little after adjustment for birth year, province, and urban/rural marriage location. Overall, results provide little support for a strong additive genetic fertility-longevity trade-off and instead highlight shared genetic influences on reproductive timing and viability