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Genetic and environmental perturbations lead to regulatory decoherence.

eLife | 2019

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.

Pubmed ID: 30834892 RIS Download

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Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: F31 HL127921
  • Agency: European Research Council, International
    Id: 742927
  • Agency: Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals, International
    Id: X51001
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG006399
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL028481
  • Agency: Suomen Akatemia, International
    Id: 117787 (Gendi)
  • Agency: Horizon 2020 Framework Programme, International
    Id: 755320
  • Agency: Suomen Akatemia, International
    Id: 41071 (Skidi)
  • Agency: Suomen Akatemia, International
    Id: 134309 (Eye)
  • Agency: Suomen Akatemia, International
    Id: 124282
  • Agency: Suomen Akatemia, International
    Id: 286284
  • Agency: Suomen Akatemia, International
    Id: 121584
  • Agency: Suomen Akatemia, International
    Id: 126925
  • Agency: NIGMS NIH HHS, United States
    Id: GM124881
  • Agency: NIGMS NIH HHS, United States
    Id: F31HL127921
  • Agency: National Health and Medical Research Council, International
    Id: APP1158958
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM124881
  • Agency: Helen Hay Whitney Foundation, International
    Id: Postdoctoral Fellowship
  • Agency: Suomen Akatemia, International
    Id: 129378 (Salve)
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL095056
  • Agency: NHLBI NIH HHS, United States
    Id: K25 HL121295
  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES029929

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RRID:SCR_007210

The American Heart Association (AHA) publishes medical scientific statements on various cardiovascular disease and stroke topics. AHA volunteer scientists and healthcare professionals write the papers. The statements are supported by scientific studies published in recognized journals and have a rigorous review and approval process. Scientific statements generally include a review of data available on a specific subject, an evaluation on its relationship to overall cardiovascular disease science, and often an American Heart Association position on the basis of that evaluation. The American Heart Association sponsors accredited scientific conferences and professional development seminars to disseminate new and emerging scientific knowledge and stimulate discussion on future research and the application of knowledge. Keywords: Heart, Cardiovascular, Disease, Stroke, Volunteer, Scientist, Healthcare, Development, Knowledge,

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