Dataset Information

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

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Avinun R

PROVIDER: S-EPMC5955809 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Avinun Reut R Nevo Adam A Knodt Annchen R AR Elliott Maxwell L ML Hariri Ahmad R AR

Biological psychiatry 20171116 2

<h4>Background</h4>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 robu ...[more]

PMID: 29279201

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Project description:Maladaptive social information processing, such as hostile attributional bias and aggressive response generation, is associated with childhood maladjustment. Although social information processing problems are correlated with heightened physiological responses to social threat, few studies have examined their associations with neural threat circuitry, specifically amygdala activation to social threat.A cohort of 310 boys participated in an ongoing longitudinal study and completed questionnaires and laboratory tasks assessing their social and cognitive characteristics the boys were between 10 and 12 years of age. At age 20, 178 of these young men underwent functional magnetic resonance imaging and a social threat task. At age 22, adult criminal arrest records and self-reports of impulsiveness were obtained.Path models indicated that maladaptive social information-processing at ages 10 and 11 predicted increased left amygdala reactivity to fear faces, an ambiguous threat, at age 20 while accounting for childhood antisocial behavior, empathy, IQ, and socioeconomic status. Exploratory analyses indicated that aggressive response generation - the tendency to respond to threat with reactive aggression - predicted left amygdala reactivity to fear faces and was concurrently associated with empathy, antisocial behavior, and hostile attributional bias, whereas hostile attributional bias correlated with IQ. Although unrelated to social information-processing problems, bilateral amygdala reactivity to anger faces at age 20 was unexpectedly predicted by low IQ at age 11. Amygdala activation did not mediate associations between social information processing and number of criminal arrests, but both impulsiveness at age 22 and arrests were correlated with right amygdala reactivity to anger facial expressions at age 20.Childhood social information processing and IQ predicted young men's amygdala response to threat a decade later, which suggests that childhood social-cognitive characteristics are associated with the development of neural threat processing and adult adjustment.

Dataset Information

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

Publications

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

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