Abstract Details

Title Intrinsic amygdala connectivity as an endophenotype for social behavior: A novel SNP affecting CSMD1 increases amygdala connectivity and prosocial behavior in a GWAS meta-analysis.

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-005

Objective To discern whether large-scale amygdala networks could serve as endophenotypes enabling the discovery of novel genetic variants that influence the development of socioemotional behaviors.

Background The amygdala is a hub for social and emotional information with diverse targets including cortical and subcortical structures involved in perceiving social cues, affiliating with friends, and avoiding foes. In the field of imaging genetics, the amygdala’s structural and functional properties have become a major focus, but its connectional properties have received little attention.

Design/Methods We performed a genome-wide association study meta-analysis of two large adolescent cohorts, IMAGEN and the Philadelphia Neurodevelopmental Cohort, followed by genotype phenotype analyses in independent subgroups of these cohorts, and functional validation analyses using separate databases in humans and across species.

Results Leveraging a resting-state model of whole-brain amygdala connectivity that generates three functionally and anatomically distinct circuits, we identified a novel genome-wide significant polymorphism (rs10105357). This polymorphism both drives amygdala connectivity within its medial network, which is implicated in promoting affiliative behaviors, and also predicts an increase in prosocial behaviors in an independent sample. Similarly, exploratory analyses of the top suggestive polymorphisms (rs35192025 and rs17671156) for the other two amygdala circuits also significantly influence behaviors referable to the function of each respective circuit, including bullying behaviors and social perception. Using the Mayo eGWAS, we found that rs10105357 acts as a significant expression quantitative trait locus for CSMD1 in the temporal cortex. Finally, we validated these findings within and across species using the Allen Human and Mouse Brain Atlases with compelling recapitulation of both the connectivity and genetic architecture of the amygdala.

Conclusions

These findings are the first to suggest that the amygdala’s connectional architecture can be used as an endophenotype for normal variation in socioemotional behavior, perhaps fundamental to the evolutionarily conserved functions needed to manage the demands of a complex social life.

Authors/Disclosures
Kevin Bickart, MD, PhD (UCLA) PRESENTER	Dr. Bickart has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Michael Greicius, MD (Stanford University)	Dr. Greicius has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acelot.

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