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Article: Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes

TitleMeta-analyses of genome-wide linkage scans of anxiety-related phenotypes
Authors
KeywordsAnxiety
Linkage
Meta-Analysis
Neuroticism
Panic Disorder
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg
Citation
European Journal Of Human Genetics, 2012, v. 20 n. 10, p. 1078-1084 How to Cite?
AbstractGenetic factors underlying trait neuroticism, reflecting a tendency towards negative affective states, may overlap genetic susceptibility for anxiety disorders and help explain the extensive comorbidity amongst internalizing disorders. Genome-wide linkage (GWL) data from several studies of neuroticism and anxiety disorders have been published, providing an opportunity to test such hypotheses and identify genomic regions that harbor genes common to these phenotypes. In all, 11 independent GWL studies of either neuroticism (n8) or anxiety disorders (n3) were collected, which comprised of 5341 families with 15 529 individuals. The rank-based genome scan meta-analysis (GSMA) approach was used to analyze each trait separately and combined, and global correlations between results were examined. False discovery rate (FDR) analysis was performed to test for enrichment of significant effects. Using 10 cM intervals, bins nominally significant for both GSMA statistics, P SR and P OR, were found on chromosomes 9, 11, 12, and 14 for neuroticism and on chromosomes 1, 5, 15, and 16 for anxiety disorders. Genome-wide, the results for the two phenotypes were significantly correlated, and a combined analysis identified additional nominally significant bins. Although none reached genome-wide significance, an excess of significant P SR P-values were observed, with 12 bins falling under a FDR threshold of 0.50. As demonstrated by our identification of multiple, consistent signals across the genome, meta-analytically combining existing GWL data is a valuable approach to narrowing down regions relevant for anxiety-related phenotypes. This may prove useful for prioritizing emerging genome-wide association data for anxiety disorders. © 2012 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/175993
ISSN
2015 Impact Factor: 4.58
2015 SCImago Journal Rankings: 2.077
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWebb, BTen_US
dc.contributor.authorGuo, AYen_US
dc.contributor.authorMaher, BSen_US
dc.contributor.authorZhao, Zen_US
dc.contributor.authorVan Den Oord, EJen_US
dc.contributor.authorKendler, KSen_US
dc.contributor.authorRiley, BPen_US
dc.contributor.authorGillespie, NAen_US
dc.contributor.authorPrescott, CAen_US
dc.contributor.authorMiddeldorp, CMen_US
dc.contributor.authorWillemsen, Gen_US
dc.contributor.authorDe Geus, EJCen_US
dc.contributor.authorHottenga, JJen_US
dc.contributor.authorBoomsma, DIen_US
dc.contributor.authorSlagboom, EPen_US
dc.contributor.authorWray, NRen_US
dc.contributor.authorMontgomery, GWen_US
dc.contributor.authorMartin, NGen_US
dc.contributor.authorWright, MJen_US
dc.contributor.authorHeath, ACen_US
dc.contributor.authorMadden, PAen_US
dc.contributor.authorGelernter, Jen_US
dc.contributor.authorKnowles, JAen_US
dc.contributor.authorHamilton, SPen_US
dc.contributor.authorWeissman, MMen_US
dc.contributor.authorFyer, AJen_US
dc.contributor.authorHuezoDiaz, Pen_US
dc.contributor.authorMcguffin, Pen_US
dc.contributor.authorFarmer, Aen_US
dc.contributor.authorCraig, IWen_US
dc.contributor.authorLewis, Cen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorCrowe, RRen_US
dc.contributor.authorFlint, Jen_US
dc.contributor.authorHettema, JMen_US
dc.date.accessioned2012-11-26T09:03:35Z-
dc.date.available2012-11-26T09:03:35Z-
dc.date.issued2012en_US
dc.identifier.citationEuropean Journal Of Human Genetics, 2012, v. 20 n. 10, p. 1078-1084en_US
dc.identifier.issn1018-4813en_US
dc.identifier.urihttp://hdl.handle.net/10722/175993-
dc.description.abstractGenetic factors underlying trait neuroticism, reflecting a tendency towards negative affective states, may overlap genetic susceptibility for anxiety disorders and help explain the extensive comorbidity amongst internalizing disorders. Genome-wide linkage (GWL) data from several studies of neuroticism and anxiety disorders have been published, providing an opportunity to test such hypotheses and identify genomic regions that harbor genes common to these phenotypes. In all, 11 independent GWL studies of either neuroticism (n8) or anxiety disorders (n3) were collected, which comprised of 5341 families with 15 529 individuals. The rank-based genome scan meta-analysis (GSMA) approach was used to analyze each trait separately and combined, and global correlations between results were examined. False discovery rate (FDR) analysis was performed to test for enrichment of significant effects. Using 10 cM intervals, bins nominally significant for both GSMA statistics, P SR and P OR, were found on chromosomes 9, 11, 12, and 14 for neuroticism and on chromosomes 1, 5, 15, and 16 for anxiety disorders. Genome-wide, the results for the two phenotypes were significantly correlated, and a combined analysis identified additional nominally significant bins. Although none reached genome-wide significance, an excess of significant P SR P-values were observed, with 12 bins falling under a FDR threshold of 0.50. As demonstrated by our identification of multiple, consistent signals across the genome, meta-analytically combining existing GWL data is a valuable approach to narrowing down regions relevant for anxiety-related phenotypes. This may prove useful for prioritizing emerging genome-wide association data for anxiety disorders. © 2012 Macmillan Publishers Limited. All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhgen_US
dc.relation.ispartofEuropean Journal of Human Geneticsen_US
dc.subjectAnxietyen_US
dc.subjectLinkageen_US
dc.subjectMeta-Analysisen_US
dc.subjectNeuroticismen_US
dc.subjectPanic Disorderen_US
dc.titleMeta-analyses of genome-wide linkage scans of anxiety-related phenotypesen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ejhg.2012.47en_US
dc.identifier.pmid22473089-
dc.identifier.scopuseid_2-s2.0-84866547366en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84866547366&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue10en_US
dc.identifier.spage1078en_US
dc.identifier.epage1084en_US
dc.identifier.isiWOS:000309166800011-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridWebb, BT=7201511256en_US
dc.identifier.scopusauthoridGuo, AY=55159333500en_US
dc.identifier.scopusauthoridMaher, BS=7006500978en_US
dc.identifier.scopusauthoridZhao, Z=7404147874en_US
dc.identifier.scopusauthoridVan Den Oord, EJ=7005835163en_US
dc.identifier.scopusauthoridKendler, KS=35396760800en_US
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dc.identifier.scopusauthoridWray, NR=7006428088en_US
dc.identifier.scopusauthoridMontgomery, GW=8739667300en_US
dc.identifier.scopusauthoridMartin, NG=35376988300en_US
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dc.identifier.scopusauthoridGelernter, J=55156801600en_US
dc.identifier.scopusauthoridKnowles, JA=55331056600en_US
dc.identifier.scopusauthoridHamilton, SP=7402244945en_US
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dc.identifier.scopusauthoridFyer, AJ=7005687422en_US
dc.identifier.scopusauthoridHuezoDiaz, P=6506170044en_US
dc.identifier.scopusauthoridMcGuffin, P=22954119700en_US
dc.identifier.scopusauthoridFarmer, A=55159353600en_US
dc.identifier.scopusauthoridCraig, IW=7102548208en_US
dc.identifier.scopusauthoridLewis, C=7402975073en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
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dc.identifier.scopusauthoridFlint, J=55158502000en_US
dc.identifier.scopusauthoridHettema, JM=6701477910en_US
dc.identifier.citeulike10546814-

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