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 x 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P = 2.86 x 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.

Authors	Martin, Nick; Otowa, Takeshi; Lee, Minyoung; Hartman, Catharina; Oldehinkel, Albertine; Preisig, Martin; Grabe, Hans Joergen; Middeldorp, Christel; Penninx, Brenda; Boomsma, Dorret; Montgomery, Grant; Wray, Naomi; Tiemeier, Henning; Hettema, John
Journal	MOLECULAR PSYCHIATRY
Pages	1391-1399
Volume	21
Date	1/10/2016
Grant ID	R01MH87646
Funding Body	NIH Grant
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/mp.2015.197