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Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry.

Publication ,  Journal Article
van der Merwe, C; Jahanshad, N; Cheung, JW; Mufford, M; Groenewold, NA; Koen, N; Ramesar, R; Dalvie, S; ENIGMA Consortium PGC-PTSD, ; Hibar, DP ...
Published in: J Affect Disord
February 15, 2019

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.

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Published In

J Affect Disord

DOI

EISSN

1573-2517

Publication Date

February 15, 2019

Volume

245

Start / End Page

885 / 896

Location

Netherlands

Related Subject Headings

  • Stress Disorders, Post-Traumatic
  • Risk Factors
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neural Pathways
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

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van der Merwe, C., Jahanshad, N., Cheung, J. W., Mufford, M., Groenewold, N. A., Koen, N., … Stein, D. J. (2019). Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry. J Affect Disord, 245, 885–896. https://doi.org/10.1016/j.jad.2018.11.082
Merwe, Celia van der, Neda Jahanshad, Josh W. Cheung, Mary Mufford, Nynke A. Groenewold, Nastassja Koen, Rajkumar Ramesar, et al. “Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry.J Affect Disord 245 (February 15, 2019): 885–96. https://doi.org/10.1016/j.jad.2018.11.082.
van der Merwe C, Jahanshad N, Cheung JW, Mufford M, Groenewold NA, Koen N, et al. Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry. J Affect Disord. 2019 Feb 15;245:885–96.
van der Merwe, Celia, et al. “Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry.J Affect Disord, vol. 245, Feb. 2019, pp. 885–96. Pubmed, doi:10.1016/j.jad.2018.11.082.
van der Merwe C, Jahanshad N, Cheung JW, Mufford M, Groenewold NA, Koen N, Ramesar R, Dalvie S, ENIGMA Consortium PGC-PTSD, Knowles JA, Hibar DP, Nievergelt CM, Koenen KC, Liberzon I, Ressler KJ, Medland SE, Morey RA, Thompson PM, Stein DJ. Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry. J Affect Disord. 2019 Feb 15;245:885–896.
Journal cover image

Published In

J Affect Disord

DOI

EISSN

1573-2517

Publication Date

February 15, 2019

Volume

245

Start / End Page

885 / 896

Location

Netherlands

Related Subject Headings

  • Stress Disorders, Post-Traumatic
  • Risk Factors
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neural Pathways
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genome-Wide Association Study
  • Genetic Variation