title: Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study.
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.
authors.affiliation: Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jacob J E
authors.initials: JJ
authors.lastname: Koopman
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.|University of Applied Sciences Leiden, Leiden, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Pijpe
authors.affiliation: Section of Medical Statistics, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Böhringer
authors.affiliation: Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.|Leyden Academy on Vitality and Ageing, Leiden, the Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: van Bodegom
authors.affiliation: Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ulrika K
authors.initials: UK
authors.lastname: Eriksson
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hernando
authors.initials: H
authors.lastname: Sanchez-Faddeev
authors.affiliation: Department of Clinical Laboratory Sciences, School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana.
authors.forename: Juventus B
authors.initials: JB
authors.lastname: Ziem
authors.affiliation: Laboratory of Genetics, Wageningen University, Wageningen, the Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Zwaan
authors.affiliation: Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: de Knijff
authors.affiliation: Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.|Department of Public Health and Center of Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005298:Fertility / Q000235:genetics*; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D005869:Ghana; D006801:Humans; D007231:Infant, Newborn; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D055815:Young Adult
keywords: Africa; SNP; aging; evolution; fertility; gene; human; life history; survival