Abstract
Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans.
Highlights
Age patterns of survival and fertility vary widely across species [1]
We investigate genetic variants that determine life history through variation in survival and fertility in a traditional rural African population that lives in such an adverse environment
We conducted a large-scale candidate gene study using a high density of SNPs
Summary
Age patterns of survival and fertility vary widely across species [1]. During evolution, natural selection has shaped these age patterns, referred to as life histories, so to optimise the fitness of each species by maximising reproduction [2]. Several genetic pathways have been found in animals that regulate survival and fertility, including the signalling cascade of growth hormone (GH), insulinlike growth factor 1 (IGF1), and insulin, signalling by target of rapamycin (TOR), DNA repair mechanisms, immune regulation, and telomere maintenance [3, 4]. These pathways have been discovered mostly in studies on mutant animal models, but likely contribute to variation in survival and fertility in wild-type animals as well [5, 6]. Genetic variants have been described as determinants of human infertility [12, 13], but have rarely been studied for variation in human fertility [14]
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