TY - JOUR

T1 - Genetic variants determining survival and fertility in an adverse African environment

T2 - a population-based large-scale candidate gene association study

AU - Koopman, Jacob J E

AU - Pijpe, Jeroen

AU - Böhringer, Stefan

AU - van Bodegom, David

AU - Eriksson, Ulrika K

AU - Sanchez-Faddeev, Hernando

AU - Ziem, Juventus B

AU - Zwaan, Bas

AU - Slagboom, P Eline

AU - de Knijff, Peter

AU - Westendorp, Rudi G J

PY - 2016/6/27

Y1 - 2016/6/27

N2 - 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.

AB - 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.

U2 - 10.18632/aging.100986

DO - 10.18632/aging.100986

M3 - Journal article

C2 - 27356285

VL - 8

SP - 1364

EP - 1383

JO - Aging

JF - Aging

SN - 1945-4589

IS - 7

ER -