Gene-environment interaction in the association of residential greenness and 25(OH) vitamin D

Abstract

There is increasing awareness for beneficial health effects of green space surrounding the home, but the underlying mechanisms are not yet fully understood and challenging to study given the correlation with other exposures. Here, the association of residential greenness and vitamin D including a gene-environment interaction is investigated. 25-hydroxyvitamin D (25(OH)D) was measured by electrochemiluminescence at ages 10 and 15 years in participants of two German birth cohorts GINIplus and LISA. Greenness was measured using the Landsat-derived Normalized Difference Vegetation Index (NDVI) in a 500 m buffer surrounding the home. Linear and logistic regression models were applied at both time points adjusted for several covariates (N_10Y = 2,504, N_15Y = 2,613). In additional analyses vitamin D-related genes, physical activity, time spent outdoors, supplements, and measurement season were investigated as potential confounders or effect modifiers. A 1.5-SD increase in NDVI was significantly associated with increased 25(OH)D values at ages 10 and 15 years (β_10y = 2.41 nmol/l, p=<0.01; β_15y = 2.03 nmol/l, p = 0.02). In stratified analyses, the associations were not seen in participants spending more than 5 h/day outside in summer, having a high physical activity level, taking supplements, or being examined during the winter season. In a subset (n = 1,732) with genetic data, a significant gene-environment interaction of NDVI with CYP2R1, an upstream gene in 25(OH)D synthesis, was observed at age 10 years. When investigating 25(OH)D sufficiency, defined as values above 50 nmol/l, a 1.5-SD increase in NDVI was associated with significantly higher odds of having sufficient 25 (OH)D levels at age 10 years (OR = 1.48, 1.19-1.83). In conclusion, robust associations between residential greenness and 25 (OH)D levels were observed in children and adolescents independent of other confounders and additionally supported by the presence of a gene-environment interaction. Effects of NDVI were stronger in those having lower vitamin D levels at age 10 years due to their covariate profile or genetically lower 25(OH)D synthesis.

Keywords: 25(OH)D; Adolescents; Epidemiology; NDVI; Residential greenness; Vitamin D.