Meta-analysis of genome-wide association studies of anxiety disorders. Academic Article uri icon

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 18000 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.

published proceedings

  • Mol Psychiatry

altmetric score

  • 39.15

author list (cited authors)

  • Otowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., ... Hettema, J. M.

citation count

  • 288

complete list of authors

  • Otowa, T||Hek, K||Lee, M||Byrne, EM||Mirza, SS||Nivard, MG||Bigdeli, T||Aggen, SH||Adkins, D||Wolen, A||Fanous, A||Keller, MC||Castelao, E||Kutalik, Z||Van der Auwera, S||Homuth, G||Nauck, M||Teumer, A||Milaneschi, Y||Hottenga, J-J||Direk, N||Hofman, A||Uitterlinden, A||Mulder, CL||Henders, AK||Medland, SE||Gordon, S||Heath, AC||Madden, PAF||Pergadia, ML||van der Most, PJ||Nolte, IM||van Oort, FVA||Hartman, CA||Oldehinkel, AJ||Preisig, M||Grabe, HJ||Middeldorp, CM||Penninx, BWJH||Boomsma, D||Martin, NG||Montgomery, G||Maher, BS||van den Oord, EJ||Wray, NR||Tiemeier, H||Hettema, JM

publication date

  • October 2016