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 Detalle_Publicacion

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

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.

 Fuente: Journal of Affective Disorders Volume 245, 15 February 2019, Pages 885-896

Editorial: Elsevier

 Fecha de publicación: 15/02/2019

Nº de páginas: 11

Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.jad.2018.11.082

ISSN: 0165-0327,1573-2517

Url de la publicación: https://doi.org/10.1016/j.jad.2018.11.082

Autores/as

MERWE, CELIA VAN DER

JAHANSHAD, NEDA

CHEUNG, JOSH W.

MUFFORD, MARY

GROENEWOLD, NYNKE

KOEN, NASTASSJA

RAMESAR, RAJKUMAR

DALVIE, SHAREEFA

ENIGMA CONSORTIUM PGC-PTSD

KNOWLES, JAMES A.

HIBAR, DERREK P.

NIEVERGELT, CAROLINE M.

KOENEN, KARESTAN C.

LIBERZON, ISRAEL

RESSLER, KERRY J.

MEDLAND, SARAH E.

MOREY, RAJENDRA A.

THOMPSON, PAUL M.

STEIN, DAN J.

ROBERTO ROIZ SANTIAÑEZ