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Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity.

Publication ,  Journal Article
Avinun, R; Nevo, A; Knodt, AR; Elliott, ML; Hariri, AR
Published in: Biological psychiatry
July 2018

Low replication rates are a concern in most, if not all, scientific disciplines. In psychiatric genetics specifically, targeting intermediate brain phenotypes, which are more closely associated with putative genetic effects, was touted as a strategy leading to increased power and replicability. In the current study, we attempted to replicate previously published associations between single nucleotide polymorphisms and threat-related amygdala reactivity, which represents a robust brain phenotype not only implicated in the pathophysiology of multiple disorders, but also used as a biomarker of future risk.We conducted a literature search for published associations between single nucleotide polymorphisms and threat-related amygdala reactivity and found 37 unique findings. Our replication sample consisted of 1117 young adult volunteers (629 women, mean age 19.72 ± 1.25 years) for whom both genetic and functional magnetic resonance imaging data were available.Of the 37 unique associations identified, only three replicated as previously reported. When exploratory analyses were conducted with different model parameters compared to the original findings, significant associations were identified for 28 additional studies: eight of these were for a different contrast/laterality; five for a different gender and/or race/ethnicity; and 15 in the opposite direction and for a different contrast, laterality, gender, and/or race/ethnicity. No significant associations, regardless of model parameters, were detected for six studies. Notably, none of the significant associations survived correction for multiple comparisons.We discuss these patterns of poor replication with regard to the general strategy of targeting intermediate brain phenotypes in genetic association studies and the growing importance of advancing the replicability of imaging genetics findings.

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Published In

Biological psychiatry

DOI

EISSN

1873-2402

ISSN

0006-3223

Publication Date

July 2018

Volume

84

Issue

2

Start / End Page

148 / 159

Related Subject Headings

  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mental Disorders
  • Magnetic Resonance Imaging
  • Humans
  • Genetic Association Studies
  • Amygdala
  • 52 Psychology
  • 32 Biomedical and clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Avinun, R., Nevo, A., Knodt, A. R., Elliott, M. L., & Hariri, A. R. (2018). Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity. Biological Psychiatry, 84(2), 148–159. https://doi.org/10.1016/j.biopsych.2017.11.010
Avinun, Reut, Adam Nevo, Annchen R. Knodt, Maxwell L. Elliott, and Ahmad R. Hariri. “Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity.Biological Psychiatry 84, no. 2 (July 2018): 148–59. https://doi.org/10.1016/j.biopsych.2017.11.010.
Avinun R, Nevo A, Knodt AR, Elliott ML, Hariri AR. Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity. Biological psychiatry. 2018 Jul;84(2):148–59.
Avinun, Reut, et al. “Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity.Biological Psychiatry, vol. 84, no. 2, July 2018, pp. 148–59. Epmc, doi:10.1016/j.biopsych.2017.11.010.
Avinun R, Nevo A, Knodt AR, Elliott ML, Hariri AR. Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity. Biological psychiatry. 2018 Jul;84(2):148–159.
Journal cover image

Published In

Biological psychiatry

DOI

EISSN

1873-2402

ISSN

0006-3223

Publication Date

July 2018

Volume

84

Issue

2

Start / End Page

148 / 159

Related Subject Headings

  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mental Disorders
  • Magnetic Resonance Imaging
  • Humans
  • Genetic Association Studies
  • Amygdala
  • 52 Psychology
  • 32 Biomedical and clinical sciences