Gene-Environment Interaction of Residential Greenness and FOXO on Mortality among Older Adults

Abstract

Background The Forkhead box O (FOXO) gene is a candidate longevity gene. Residential greenness is an important built environment factor strongly associated with mortality. There was no previous study on the interaction between FOXO and residential greenness based on our knowledge. Methods We studied 3,179 participants aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We measured residential greenness by satellite derived Normalized Difference Vegetation Index (NDVI) using a 500-m radius around each residential address. We calculated contemporaneous NDVI, cumulative NDVI and changes in NDVI over time. We used adjusted Cox-proportional hazard regression models to assess main effects and interaction of FOXO SNPs and residential greenness on mortality risk. Results We found participants with two minor allele copies of FOXO3A SNPs had lower mortality risk than those with zero copy (HR: 0.803 95% CI: 0.654, 0.987 for rs4946936, HR: 0.807 95% CI: 0.669, 0.974 for rs2802292, HR: 0.803 95%CI: 0.666, 0.968 for rs2253310). We found no mortality difference among different genotypes for FOXO1A SNPs rs17630266, rs2755209 and rs2755213. Higher contemporaneous NDVI was associated with lower mortality risk (HR: 0.887 95% CI: 0.863, 0.911 for 0.1 unit of NDVI). The protective effect of NDVI was stronger among participants with two minor allele copies of rs2802292 SNP compared with the ones with zero copy (Interaction term P<0.05), while not different between participants with one copy and zero copy.Conclusions We found gene-environment interaction between FOXO and residential greenness on mortality in this population study. A higher level of greenness may interact with FOXO pathways.