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

Residential greenness is an important environmental factor that is strongly associated with mortality. To our knowledge, there was no previous study on the gene-environment interaction analysis between residential greenness and forkhead box O (FOXO) gene, a candidate longevity gene. Our sample consisted of 3179 participants aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey. Residential greenness was measured by satellite-derived normalized difference vegetation index (NDVI) using a 500-m radius around each residential location. Contemporaneous NDVI, cumulative NDVI, and changes in NDVI over time were calculated. We used Cox-proportional hazard regression models to assess the main effect and gene-environment interaction effect of FOXO single nucleotide polymorphism (SNP) and residential greenness on mortality. We found that participants carrying two minor alleles of the three studied FOXO3A SNPs had lower mortality risk than those without minor allele (hazard ratio [HR]: 0.803 95% confidence interval [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 difference in mortality among the genotypes of the other three FOXO1A SNPs (rs17630266, rs2755213, or rs2755209). Higher contemporaneous NDVI was associated with lower mortality risk (HR: 0.887 95% CI: 0.863-0.911 for 0.1-U of NDVI). The protective effect of both contemporaneous NDVI and cumulative NDVI was stronger for two minor allele carriers compared with zero minor allele carriers of the three FOXO3A SNPs. Compared with the zero minor allele genotype of the three FOXO3A SNPs, the protective effect on the mortality risk of minor allele homozygotes also increased with the increasing NDVI level at percentile 25, 50, and 75 (interaction term coefficient p < 0.05). 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.

Duke Scholars

Author Yi Zeng Medicine, Geriatrics

Author John Ji DKU Faculty