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

• Type of Material: Article
• Authors: Claudia Wigmann, IUF—Leibniz Research Institute for Environmental Medicine; Anke Hüls, Emory University; Jean Krutmann, IUF—Leibniz Research Institute for Environmental Medicine; Tamara Schikowski, IUF—Leibniz Research Institute for Environmental Medicine
• Language: English
• Date: 2022-12-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijerph192416746
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
• Volume: 19
• Issue: 24
• Grant/Funding Information: The SALIA cohort study was supported by the Ministry of the Environment of the state North Rhine-Westphalia (Düsseldorf, Germany), the Federal Ministry of the Environment (Berlin, Germany), the German Federal Ministry of Education and Research (BMBF) as well as by grants HE-4510/2-1, KR 1938/3-1, LU 691/4-1 and SCHI 1358/3-1 from the Deutsche Forschungsgemeinschaft (DFG), VT 266.1 from the German Statutory Accident Insurance (DGUV) and grant agreement number 211250 from the European Community’s Seventh Framework Program (FP7/2007-2011). Anke Hüls is supported by grant [NIEHS P30ES019776] from the HERCULES Center.
• Keywords: environmental exposure; relative contribution; REGULARIZATION; Science & Technology; CHALLENGE; EXPOSURE; ESCAPE; AIR-POLLUTION; Environmental Sciences; relative importance; EXPOSOME; Life Sciences & Biomedicine; risk score; aging; Public, Environmental & Occupational Health; GENOME-WIDE ASSOCIATION; Environmental Sciences & Ecology; exposome; SELECTION; LUNG-FUNCTION; USE REGRESSION-MODELS
• Research Categories: Health Sciences, Public Health

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.