Journal Article

Genetic and environmental perturbations lead to regulatory decoherence

Raitoharju, Emma, Ala-Korpela, Mika, Mononen, Nina, Subramaniam, Meena, Kähönen, Mika, Ko, Arthur, Zaitlen, Noah, Lea, Amanda, Pajukanta, Päivi, Lehtimäki, Terho, Seppälä, Ilkka, Raitakari, Olli T, Ayroles, Julien F

2019

Overview

Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (infection and disease) lead to a systematic loss of correlation, which we define as 'decoherence'. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we demonstrate that correlation itself is under genetic control by mapping hundreds of 'correlation quantitative trait loci (QTLs)'. Together, this work furthers our understanding of how and why coordinated biological processes break down, and points to a potential role for decoherence in disease. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter ).

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Binomial distribution / co-expression / Computer Simulation / decanalization / decoherence / Environmental Exposure / Epidemiology / Gene expression / Gene Expression Profiling / Gene mapping / Genetic control / Genetic diversity / Genetic Variation / Genetics and Genomics / Genomics / Health care / Hospitals / Human Biology and Medicine / Humans / Individuality / Information sharing / Laboratories / Magnetic Resonance Spectroscopy / Metabolic Diseases - genetics / Metabolic Diseases - physiopathology / Metabolic syndrome / Metabolites / Metabolome / NMR / Nuclear magnetic resonance / Physiology / Preventive medicine / Quantitative Trait Loci / Research Communication