Disentangling genetic and environmental risk factors for individual diseases from multiplex comorbidity networks

TL;DR

This study introduces a quantitative method to distinguish the contributions of genetic and environmental factors to the development of 358 diseases by analyzing multiplex comorbidity networks derived from extensive patient data.

Contribution

It presents a novel multilayer network approach that quantifies the relative importance of genetic and environmental mechanisms for individual diseases, integrating diverse biological data with disease co-occurrence.

Findings

Most diseases are genetically dominated.

Environmental factors are prevalent in depression, cancer, dermatitis.

Diseases rarely involve multiple mechanism types.

Abstract

Most disorders are caused by a combination of multiple genetic and/or environmental factors. If two diseases are caused by the same molecular mechanism, they tend to co-occur in patients. Here we provide a quantitative method to disentangle how much genetic or environmental risk factors contribute to the pathogenesis of 358 individual diseases, respectively. We pool data on genetic, pathway-based, and toxicogenomic disease-causing mechanisms with disease co-occurrence data obtained from almost two million patients. From this data we construct a multilayer network where nodes represent disorders that are connected by links that either represent phenotypic comorbidity of the patients or the involvement of a certain molecular mechanism. From the similarity of phenotypic and mechanism-based networks for each disorder we derive measure that allows us to quantify the relative importance of various molecular mechanisms for a given disease. We find that most diseases are dominated by genetic risk factors, while environmental influences prevail for disorders such as depressions, cancers, or dermatitis. Almost never we find that more than one type of mechanisms is involved in the pathogenesis of diseases.