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. 2016 Jul;8(7):1364-83.
doi: 10.18632/aging.100986.

Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study

Jacob J E Koopman  1 , Jeroen Pijpe  2   3 , Stefan Böhringer  4 , David van Bodegom  1   5 , Ulrika K Eriksson  1 , Hernando Sanchez-Faddeev  2 , Juventus B Ziem  6 , Bas Zwaan  7 , P Eline Slagboom  8 , Peter de Knijff  2 , Rudi G J Westendorp  1   9
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Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study

Jacob J E Koopman et al. Aging (Albany NY). 2016 Jul.

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.

Keywords: Africa; SNP; aging; evolution; fertility; gene; human; life history; survival.

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Conflict of interest statement

statement The authors have no conflict of interests to declare.

Figures

Figure 1
Figure 1. Summary of the exclusions and inclusions of individuals and SNPs
Figure 2
Figure 2. Manhattan plots assessing the associations of SNPs with survival
(A) Manhattan plot assessing the associations of SNPs with survival between newborns and old individuals aged 60 years or over. (B) Manhattan plot assessing the associations of SNPs with survival between newborns and middle-aged adults of fertile ages from 20 through 44 years. (C) Manhattan plot assessing the associations of SNPs with survival between middle-aged adults of fertile ages from 20 through 44 years and old individuals aged 60 years or over. The analyses were adjusted for sex. The level of significance is 1.23 × 10−5, indicated by the red lines.
Figure 3
Figure 3. Manhattan plots assessing the associations of SNPs with fertility in women
(A) Manhattan plot assessing the associations of SNPs with observed fertility in middle-aged women of fertile ages from 20 through 44 years. The level of significance is 1.61 × 10−5, indicated by the red line. (B) Manhattan plot assessing the associations of SNPs with reported fertility in postmenopausal women aged 45 years and older. The level of significance is 1.23 × 10−5, indicated by the red line.
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