Meta-analysis of genome-wide association studies of anxiety disorders.
Mol Psychiatry
; 21(10): 1391-9, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-26754954
ABSTRACT
Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos de Ansiedade
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Mol Psychiatry
Assunto da revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos