Genetic links between post-reproductive lifespan and family size in Framingham.

Abstract

BACKGROUND AND OBJECTIVES: Is there a trade-off between children ever born (CEB) and post-reproductive lifespan in humans? Here, we report a comprehensive analysis of reproductive trade-offs in the Framingham Heart Study (FHS) dataset using phenotypic and genotypic correlations and a genome-wide association study (GWAS) to look for single-nucleotide polymorphisms (SNPs) that are related to the association between CEB and lifespan. METHODOLOGY: We calculated the phenotypic and genetic correlations of lifespan with CEB for men and women in the Framingham dataset, and then performed a GWAS to search for SNPs that might affect the relationship between post-reproductive lifespan and CEB. RESULTS: We found significant negative phenotypic correlations between CEB and lifespan in both women (rP = -0.133, P < 0.001) and men (rP = -0. 079, P = 0.036). The genetic correlation was large, highly significant and strongly negative in women (rG = -0.877, P = 0.009) in a model without covariates, but not in men (P = 0.777). The GWAS identified five SNPs associated with the relationship between CEB and post-reproductive lifespan in women; some are near genes that have been linked to cancer. None were identified in men. CONCLUSIONS AND IMPLICATIONS: We identified several SNPs for which the relationship between CEB and post-reproductive lifespan differs by genotype in women in the FHS who were born between 1889 and 1958. That result was not robust to changes in the sample. Further studies on larger samples are needed to validate the antagonistic pleiotropy of these genes.