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

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...

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Main Authors:	Otowa, Takeshi, Maher, Brion S., Aggen, Steven H., McClay, Joseph L., van den Oord, Edwin J., Hettema, John M.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229211/

id	pubmed-4229211
recordtype	oai_dc
spelling	pubmed-42292112014-11-18 Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples Otowa, Takeshi Maher, Brion S. Aggen, Steven H. McClay, Joseph L. van den Oord, Edwin J. Hettema, John M. Research Article 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. Public Library of Science 2014-11-12 /pmc/articles/PMC4229211/ /pubmed/25390645 http://dx.doi.org/10.1371/journal.pone.0112559 Text en © 2014 Otowa et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Otowa, Takeshi Maher, Brion S. Aggen, Steven H. McClay, Joseph L. van den Oord, Edwin J. Hettema, John M.
spellingShingle	Otowa, Takeshi Maher, Brion S. Aggen, Steven H. McClay, Joseph L. van den Oord, Edwin J. Hettema, John M. Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
author_facet	Otowa, Takeshi Maher, Brion S. Aggen, Steven H. McClay, Joseph L. van den Oord, Edwin J. Hettema, John M.
author_sort	Otowa, Takeshi
title	Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
title_short	Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
title_full	Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
title_fullStr	Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
title_full_unstemmed	Genome-Wide and Gene-Based Association Studies of Anxiety Disorders in European and African American Samples
title_sort	genome-wide and gene-based association studies of anxiety disorders in european and african american samples
description	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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229211/
_version_	1613155637029502976

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

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