Estimating the Relative Contribution of Environmental and Genetic Risk Factors to Different Aging Traits by Combining Correlated Variables into Weighted Risk Scores

Abstract

Genetic and exposomal factors contribute to the development of human aging. For example, genetic polymorphisms and exposure to environmental factors (air pollution, tobacco smoke, etc.) influence lung and skin aging traits. For prevention purposes it is highly desirable to know the extent to which each category of the exposome and genetic factors contribute to their development. Estimating such extents, however, is methodologically challenging, mainly because the predictors are often highly correlated. Tackling this challenge, this article proposes to use weighted risk scores to assess combined effects of categories of such predictors, and a measure of relative importance to quantify their relative contribution. The risk score weights are determined via regularized regression and the relative contributions are estimated by the proportion of explained variance in linear regression. This approach is applied to data from a cohort of elderly Caucasian women investigated in 2007–2010 by estimating the relative contribution of genetic and exposomal factors to skin and lung aging. Overall, the models explain 17% (95% CI: [9%, 28%]) of the outcome’s variance for skin aging and 23% ([11%, 34%]) for lung function parameters. For both aging traits, genetic factors make up the largest contribution. The proposed approach enables us to quantify and rank contributions of categories of exposomal and genetic factors to human aging traits and facilitates risk assessment related to common human diseases in general. Obtained rankings can aid political decision making, for example, by prioritizing protective measures such as limit values for certain exposures.

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

“…Thus, differently from internal organs, in the skin stroma alteration can precede (or act independently) tumor onset moving as a driver of the tumorigenic process. and UVB represent [55] the major cutaneous stressful factor; however, smoking, pollution, and diet might also play a relevant role [56][57][58]. Interestingly, while the effect of most of the environmental factors (environmental exposome) largely depends on lifestyle, the side effect of ultraviolet exposition mostly depends on skin phenotype [59][60][61].…”

“…Other genetic variables involve SNPs of genes related to susceptibility to oxidative stress [ 55 ]. There is no doubt that ultraviolet (UV) irradiation exposure, in particular, UVA and UVB represent [ 55 ] the major cutaneous stressful factor; however, smoking, pollution, and diet might also play a relevant role [ 56 , 57 , 58 ]. Interestingly, while the effect of most of the environmental factors (environmental exposome) largely depends on lifestyle, the side effect of ultraviolet exposition mostly depends on skin phenotype [ 59 , 60 , 61 ].…”