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Neurosci Lett. 2009 Mar 6;452(1):84-6. doi: 10.1016/j.neulet.2009.01.036. Epub 2009 Jan 19.

Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance.

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Anxiety Disorders Program, Hospital de ClĂ­nicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, Department of Psychiatry, Luiz Manoel Gonzaga 630/11, 90470-280 Porto Alegre, RS, Brazil.


Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p=0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r(2)=0.022; nominal p=0.022) and PD (OR=2.64; nominal p=0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association.

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