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Beyond genotype: serotonin transporter epigenetic modification predicts human brain function

Nature Neuroscience volume 17, pages 11531155 (2014) | Download Citation

Abstract

We examined epigenetic regulation in regards to behaviorally and clinically relevant human brain function. Specifically, we found that increased promoter methylation of the serotonin transporter gene predicted increased threat-related amygdala reactivity and decreased mRNA expression in postmortem amygdala tissue. These patterns were independent of functional genetic variation in the same region. Furthermore, the association with amygdala reactivity was replicated in a second cohort and was robust to both sampling methods and age.

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Acknowledgements

We thank B. Brigidi, K. Faig, A. Gorka, S. Jacobson, A. Knodt, B. Williams and K. Sugden for their assistance in DNS data collection and analysis, and J. Hanson for his assistance in figure preparation. The Duke Neurogenetics Study is supported by Duke University and National Institute on Drug Abuse grant DA03369. The Teen Alcohol Outcomes Study was supported by AA016274 and ongoing support from the Dielmann Family (D.E.W.). Y.S.N. receives support through a Howard Hughes Medical Institute International Student Research fellowship. A.R.H. receives support through National Institute on Drug Abuse grants DA033369 and DA031579. K.C.K. receives support through National Institute of Mental Health grants MH078928 and MH093612. E.S. receives support through National Institute of Mental Health grants MH084060 and MH077159.

Author information

Affiliations

  1. Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, and Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina, USA.

    • Yuliya S Nikolova
    •  & Ahmad R Hariri
  2. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.

    • Karestan C Koenen
    •  & Sandro Galea
  3. Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

    • Chiou-Miin Wang
  4. Department of Psychiatry, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Marianne L Seney
    •  & Etienne Sibille
  5. Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

    • Douglas E Williamson

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Contributions

Y.S.N. designed the study, participated in the collection of the neuroimaging and genetic data for the discovery cohort, conducted all of the statistical analyses, and wrote the manuscript with A.R.H. K.C.K. and S.G. designed and coordinated the methylation analyses in the discovery cohort. C.-M.W. developed and performed the methylation assays in the replication and postmortem cohorts. M.L.S. conducted the quantitative PCR in the postmortem cohort. E.S. designed the parent protocol, supervised quantitative PCR experiments and coordinated methylation analyses in the postmortem cohort. D.E.W. designed the parent protocol for the replication cohort and coordinated the methylation assays in both the replication and postmortem cohorts. A.R.H. designed the study, coordinated all analyses and wrote the manuscript with Y.S.N. He also designed the parent protocol for the discovery cohort and the neuroimaging protocol for the replication cohort. All of the authors provided feedback on the manuscript and approved its final version.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yuliya S Nikolova.

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DOI

https://doi.org/10.1038/nn.3778

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