Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples

Authors

Takeshi Otowa, Virginia Commonwealth University, University of Tokyo
Brion S. Maher, Johns Hopkins Bloomberg School of Public Health
Steven H. Aggen, Virginia Commonwealth UniversityFollow
Joseph L. McClay, Virginia Commonwealth UniversityFollow
Edwin J. van den Oord, Virginia Commonwealth UniversityFollow
John M. Hettema, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

PLoS ONE

Volume

9

Issue

11

DOI of Original Publication

10.1371/journal.pone.0112559

Comments

Originally published at http://dx.doi.org/10.1371/journal.pone.0112559

Date of Submission

November 2015

Abstract

Anxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540 European American and 849 African American subjects) genotyped on the Affymetrix GeneChip 6.0 array. We applied two phenotypic approaches: (1) categorical case-control comparisons (CC) based upon psychiatric diagnoses, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. Linear and logistic models were used to analyse the association with ADs using FS and CC traits, respectively. At the single locus level, no genome-wide significant association was found. A trans-population gene-based meta-analysis across both ethnic subsamples using FS identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12) with genome-wide significance (false discovery rate (FDR] <5%). At the pathway level, several terms such as transcription regulation, cytokine binding, and developmental process were significantly enriched in ADs (FDR <5%). Our approaches studying ADs as quantitative traits and utilizing the full GWAS data may be useful in identifying susceptibility genes and pathways for ADs.

Rights

© 2014 Otowa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Psychiatry Publications