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

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http://eprints.org/relation/isVersionOf https://pure.iiasa.ac.at/id/document/75458 http://eprints.org/relation/isVolatileVersionOf https://pure.iiasa.ac.at/id/document/75458 http://eprints.org/relation/issmallThumbnailVersionOf https://pure.iiasa.ac.at/id/document/75458 archive 2 disk0/00/01/42/51 2017-01-16 13:50:47 2021-08-27 17:41:46 2017-01-16 13:50:47 article show Klimek Peter Aichberger Silke Thurner S. 1918 Disentangling genetic and environmental risk factors for individual diseases from multiplex comorbidity networks pub prog_asa environmental risk factors, individual diseases, complexity, network topology 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 multiplex 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. 2016 doi:10.1038/srep39658 307 public Scientific Reports 6 art.no.39658 TRUE 2045-2322 Foundational Research on MULTIlevel comPLEX networks and systems (MULTIPLEX, FP7 317532) FALSE yes info:eu-repo/grantAgreement/EC/FP7/317532/EU/MULTIPLEX info:eu-repo/semantics/article info:eu-repo/semantics/openAccess