University of Oulu

eLife 2019;8:e40538, doi: 10.7554/eLife.40538

Genetic and environmental perturbations lead to regulatory decoherence

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Author: Lea, Amanda1,2; Subramaniam, Meena3; Ko, Arthur4;
Organizations: 1Department of Ecology and Evolution, Princeton University, Princeton, United States
2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States
3Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, United States
4Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, United States
5Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
6Finnish Cardiovascular Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
7Department of Clinical Physiology, Tampere University, Tampere University Hospital, Tampere, Finland
8Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
9Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
10Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia
11Computational Medicine, Faculty of Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
12NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
13Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
14Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
15Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Australia
16Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, United States
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 7.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202003279478
Language: English
Published: eLife Sciences Publications, 2019
Publish Date: 2020-03-27
Description:

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 '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.

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Series: eLife
ISSN: 2050-084X
ISSN-E: 2050-084X
ISSN-L: 2050-084X
Volume: 8
Article number: e40538
DOI: 10.7554/eLife.40538
OADOI: https://oadoi.org/10.7554/eLife.40538
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: 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’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; Yrjo ¨ 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.
Copyright information: © Lea et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
  https://creativecommons.org/licenses/by/4.0/