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Am J Psychiatry. 2015 Feb 1;172(2):190-9. doi: 10.1176/appi.ajp.2014.14030311. Epub 2014 Oct 31.

Pleiotropic locus for emotion recognition and amygdala volume identified using univariate and bivariate linkage.

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From the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Conn.; the Department of Genetics, Texas Biomedical Research Institute, San Antonio; the Department of Psychiatry and the Research Imaging Institute, University of Texas Health Science Center at San Antonio; and South Texas Veterans Health System, San Antonio.



The role of the amygdala in emotion recognition is well established, and amygdala volume and emotion recognition performance have each been shown separately to be highly heritable traits, but the potential role of common genetic influences on both traits has not been explored. The authors investigated the pleiotropic influences of amygdala volume and emotion recognition performance.


In a sample of randomly selected extended pedigrees (N=858), the authors used a combination of univariate and bivariate linkage to investigate pleiotropy between amygdala volume and emotion recognition performance and followed up with association analysis.


The authors found a pleiotropic region for amygdala volume and emotion recognition performance on chromosome 4q26 (LOD score=4.40). Association analysis conducted in the region underlying the bivariate linkage peak revealed a variant meeting the corrected significance level (Bonferroni-corrected p=5.01×10(-5)) within an intron of PDE5A (rs2622497, p=4.4×10(-5)) as being jointly influential on both traits. PDE5A has been implicated previously in recognition-memory deficits and is expressed in subcortical structures that are thought to underlie memory ability, including the amygdala.


This study extends our understanding of the shared etiology between the amygdala and emotion recognition by showing that the overlap between amygdala volume and emotion recognition performance is due at least in part to common genetic influences. Moreover, this study identifies a pleiotropic locus for the two traits and an associated variant, which localizes the genetic signal even more precisely. These results, when taken in the context of previous research, highlight the potential utility of PDE5 inhibitors for ameliorating emotion recognition deficits in individuals suffering from mental or neurodegenerative illness.

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