@article{10902/15039,
year = {2019},
month = {2},
url = {http://hdl.handle.net/10902/15039},
abstract = {Background

There have been considerable recent advances in understanding the genetic architecture of anxiety disorders and posttraumatic stress disorder (PTSD), as well as the underlying neurocircuitry of these disorders. However, there is little work on the concordance of genetic variations that increase risk for these conditions, and that influence subcortical brain structures. We undertook a genome-wide investigation of the overlap between the genetic influences from single nucleotide polymorphisms (SNPs) on volumes of subcortical brain structures and genetic risk for anxiety disorders and PTSD.


Method

We obtained summary statistics of genome-wide association studies (GWAS) of anxiety disorders (Ncases=?7016, Ncontrols=?14,745), PTSD (European sample; Ncases=?2424, Ncontrols=?7113) and of subcortical brain structures (N?=?13,171). SNP Effect Concordance Analysis (SECA) and Linkage Disequilibrium (LD) Score Regression were used to examine genetic pleiotropy, concordance, and genome-wide correlations respectively. SECAs conditional false discovery was used to identify specific risk variants associated with anxiety disorders or PTSD when conditioning on brain related traits.


Results

For anxiety disorders, we found evidence of significant concordance between increased anxiety risk variants and variants associated with smaller amygdala volume. Further, by conditioning on brain volume GWAS, we identified novel variants that associate with smaller brain volumes and increase risk for disorders: rs56242606 was found to increase risk for anxiety disorders, while two variants (rs6470292 and rs683250) increase risk for PTSD, when conditioning on the GWAS of putamen volume.


Limitations

Despite using the largest available GWAS summary statistics, the analyses were limited by sample size.


Conclusions

These preliminary data indicate that there is genome wide concordance between genetic risk factors for anxiety disorders and those for smaller amygdala volume, which is consistent with research that supports the involvement of the amygdala in anxiety disorders. It is notable that a genetic variant that contributes to both reduced putamen volume and PTSD plays a key role in the glutamatergic system. Further work with GWAS summary statistics from larger samples, and a more extensive look at the genetics underlying brain circuits, is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.},
publisher = {Elsevier},
publisher = {Journal of Affective Disorders 

Volume 245, 15 February 2019, Pages 885-896},
title = {Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry},
author = {Merwe, Celia van der and Jahanshad, Neda and Cheung, Josh W. and Mufford, Mary and Groenewold, Nynke and Koen, Nastassja and Ramesar, Rajkumar and Dalvie, Shareefa and ENIGMA 
Consortium PGC-PTSD and Knowles, James A. and Hibar, Derrek P. and Nievergelt, Caroline M. and Koenen, Karestan C. and Liberzon, Israel and Ressler, Kerry J. and Medland, Sarah E. and Morey, Rajendra A. and Thompson, Paul M. and Stein, Dan J. and Roiz Santiáñez, Roberto Miguel and Crespo Facorro, Benedicto},
}