@article{d60f2424d9f747029c12108f797199c3,
title = "Genetic and environmental perturbations lead to regulatory decoherence",
abstract = "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 {\textquoteleft}decoherence{\textquoteright}. 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 {\textquoteleft}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{\textquoteright}s assessment is that all the issues have been addressed (see decision letter).",
author = "Amanda Lea and Meena Subramaniam and Arthur Ko and Terho Lehtim{\"a}ki and Emma Raitoharju and Mika K{\"a}h{\"o}nen and Ilkka Sepp{\"a}l{\"a} and Nina Mononen and Raitakari, {Olli T.} and Mika Ala-Korpela and P{\"a}ivi Pajukanta and Noah Zaitlen and Ayroles, {Julien F.}",
note = "Funding Information: We thank all volunteers who participated in the studies described here. We also thank the Ayroles lab for helpful comments on previous manuscript versions. This study was funded by National Institutes of Health (NIH) grants GM124881 to JFA, HL-095056 and HL-28481. AJL is supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation, and AK is supported by NIH grant F31HL127921. MAK is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1158958). He also works in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1). The Baker Institute is supported in part by the Victorian Government{\textquoteright}s Operational Infrastructure Support Program. The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj{\"o} Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS); European Research Council (grant 742927 for MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation. Funding Information: We thank all volunteers who participated in the studies described here. We also thank the Ayroles lab for helpful comments on previous manuscript versions. This study was funded by National Insti- tutes of Health (NIH) grants GM124881 to JFA, HL-095056 and HL-28481. AJL is supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation, and AK is supported by NIH grant F31HL127921. MAK is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1158958). He also works in a unit that is sup- ported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1). The Baker Institute is supported in part by the Victorian Government{\textquoteright}s Operational Infrastructure Support Pro- gram. The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cul- tural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj{\"o} Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS); European Research Council (grant 742927 for MULTIEPIGEN project); and Tampere University Hos- pital Supporting Foundation. Publisher Copyright: {\textcopyright} Lea et al.",
year = "2019",
month = mar,
doi = "10.7554/eLife.40538",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}