A Bio-Demographic Analysis of General, Independent, Joint, GxG and GxE Interaction Effects of FOXO Genotypes on Longevity

Yi Zeng, Duke University and Peking University
Lingguo Cheng, Peking University
Huashuai Chen, Peking University
Huiqing Cao, Peking University
Elizabeth Hauser, Duke University
Liu Yuzhi, Peking University
Zhenyu Xiao, Peking University
Qihua Tan, Southern Denmark University
Xiaoli Tian, Peking University
James W. Vaupel, Max Planck Institute for Demographic Research

We extend/apply the bio-demographic and statistical methods to genotypic/phenotypic data from 1,104 Han Chinese centenarians and 1,406 middle-age controls. Our estimates show that the genotypes of FOXO1A and FOXO3A have significantly negative and positive effects, respectively, on survival probability from middle-age to age 100+. The positive effects of FOXO3A and negative effects of FOXO1A largely compensate each other if one carries both, although FOXO3A has a stronger impact. The 10-year-follow-up cohort analysis show that, adjusted for various confounders, the positive effects of FOXO3A on survival remain statistically significant at ages 92+, but the negative effects of FOXO1A disappear; GxG interactions between FOXO1A-209 and FOXO3A-310 or FOXO3A-292 increase mortality risk by 32-36% (P<0.05); GxE interaction between FOXO1A-209 and regular exercise reduces mortality risk by 31-32% (P<0.05). The first-hand findings concerning the effects of FOXO1A and its interaction with regular exercise on longevity were generally replicated in Southern and Northern China Han women.