Genetics and Demography of the Framingham Cohorts: The Pattern of Joint Influence of Many Small-Effect Genetic Variants on Life Span and Mortality Risk

Anatoliy I. Yashin, Duke University
Deqing Wu, University of Colorado at Boulder
Konstantin G. Arbeev, Duke University
Svetlana V. Ukraintseva, Duke University

The results of recent evaluations of genome wide association (GWA) studies of complex phenotypic traits, including age at disease onset, or life span, showed that such traits are typically affected by a large number of "small-effect-low-significance" alleles, which were excluded from further analyses in traditional GWA studies. In this paper we identified alleles, having small effects on life span, or mortality risk, calculated the numbers of such alleles contained in genomes of study participants, and then evaluated their joint influence on mortality risk and life span. We showed that the joint influence of such alleles is both significant and substantial. The dependence between life span and the number of such genetic variants can be approximated by “genetic dose—life span response” relationship. The result was replicated in independent populations. This new finding will encourage revision of current methods of genetic analyses of life history traits.