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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| 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] |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112559</identifier><identifier>PMID: 25390645</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>African Americans ; African Americans - genetics ; Analysis ; Anxiety ; Anxiety Disorders - genetics ; Bioinformatics ; Bipolar disorder ; Case-Control Studies ; Chromosome 4 ; Data processing ; Environmental factors ; European Continental Ancestry Group - genetics ; Fear & phobias ; Gene regulation ; Genes ; Genetic Predisposition to Disease ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype ; Humans ; Loci ; Medicine and Health Sciences ; Mental disorders ; Meta-analysis ; Multivariate analysis ; Obsessive compulsive disorder ; Pharmacy ; Physical Sciences ; Polymorphism, Single Nucleotide ; Precision medicine ; Psychiatry ; Research and Analysis Methods ; Schizophrenia ; Studies ; Transcription</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e112559</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Otowa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Otowa et al 2014 Otowa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-cabdef41c50727c5c644b9246fde5031e68f64f884fdba27e748aa08cbe38de23</citedby><cites>FETCH-LOGICAL-c758t-cabdef41c50727c5c644b9246fde5031e68f64f884fdba27e748aa08cbe38de23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229211/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229211/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25390645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Otowa, Takeshi</creatorcontrib><creatorcontrib>Maher, Brion S</creatorcontrib><creatorcontrib>Aggen, Steven H</creatorcontrib><creatorcontrib>McClay, Joseph L</creatorcontrib><creatorcontrib>van den Oord, Edwin J</creatorcontrib><creatorcontrib>Hettema, John M</creatorcontrib><title>Genome-wide and gene-based association studies of anxiety disorders in European and African American samples</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>African Americans</subject><subject>African Americans - genetics</subject><subject>Analysis</subject><subject>Anxiety</subject><subject>Anxiety Disorders - genetics</subject><subject>Bioinformatics</subject><subject>Bipolar disorder</subject><subject>Case-Control Studies</subject><subject>Chromosome 4</subject><subject>Data processing</subject><subject>Environmental factors</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Fear & phobias</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Loci</subject><subject>Medicine and Health Sciences</subject><subject>Mental disorders</subject><subject>Meta-analysis</subject><subject>Multivariate analysis</subject><subject>Obsessive compulsive disorder</subject><subject>Pharmacy</subject><subject>Physical Sciences</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Precision medicine</subject><subject>Psychiatry</subject><subject>Research and Analysis Methods</subject><subject>Schizophrenia</subject><subject>Studies</subject><subject>Transcription</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkltr3DAQhU1padK0_6C0hkKhD97qassvgSWk6UIg0NurGEvjXS22tZXsNvn39WadsIYWih40jL45Gg4nSV5TsqC8oB-3fggdNIud73BBKGVSlk-SU1pyluWM8KdH9UnyIsYtIZKrPH-enDDJS5ILeZo0V9j5FrPfzmIKnU3X2GFWQUSbQozeOOid79LYD9ZhTH09UrcO-7vUuuiDxRBT16WXQ_A7hO5eY1kHZ8Z62eKhiNDuGowvk2c1NBFfTfdZ8v3T5beLz9n1zdXqYnmdmUKqPjNQWawFNZIUrDDS5EJUJRN5bVESTjFXdS5qpURtK2AFFkIBEGUq5Moi42fJ24PurvFRT0ZFTXPGORWq3BOrA2E9bPUuuBbCnfbg9H3Dh7WG0DvToIayyoUtDRUShKIEqMxZabhQHKUAOmqdT78NVYvWYNcHaGai85fObfTa_9KCsZLRvcC7SSD4nwPG_h8rT9Qaxq1cV_tRzLQuGr0UVEnJ8oKM1OIv1Hgsts6MUand2J8NfJgNjEyPt_0ahhj16uuX_2dvfszZ90fsBqHpN9E3wz5NcQ6KA2iCjzFg_egcJXqf9Ac39D7pekr6OPbm2PXHoYdo8z_PZfmT</recordid><startdate>20141112</startdate><enddate>20141112</enddate><creator>Otowa, Takeshi</creator><creator>Maher, Brion S</creator><creator>Aggen, Steven H</creator><creator>McClay, Joseph L</creator><creator>van den Oord, Edwin J</creator><creator>Hettema, John M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141112</creationdate><title>Genome-wide and gene-based association studies of anxiety disorders in European and African American samples</title><author>Otowa, Takeshi ; Maher, Brion S ; Aggen, Steven H ; McClay, Joseph L ; van den Oord, Edwin J ; Hettema, John M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-cabdef41c50727c5c644b9246fde5031e68f64f884fdba27e748aa08cbe38de23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>African Americans</topic><topic>African Americans - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25390645</pmid><doi>10.1371/journal.pone.0112559</doi><oa>free_for_read</oa></addata></record> |
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| subjects | African Americans African Americans - genetics Analysis Anxiety Anxiety Disorders - genetics Bioinformatics Bipolar disorder Case-Control Studies Chromosome 4 Data processing Environmental factors European Continental Ancestry Group - genetics Fear & phobias Gene regulation Genes Genetic Predisposition to Disease Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotype Humans Loci Medicine and Health Sciences Mental disorders Meta-analysis Multivariate analysis Obsessive compulsive disorder Pharmacy Physical Sciences Polymorphism, Single Nucleotide Precision medicine Psychiatry Research and Analysis Methods Schizophrenia Studies Transcription |
| title | Genome-wide and gene-based association studies of anxiety disorders in European and African American samples |
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