Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22473089
TITLE
Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes.
ABSTRACT
Genetic 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 (n=8) or anxiety disorders (n=3) 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.
DATE PUBLISHED
2012 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/04/04
entrez 2012/04/05 06:00
pubmed 2012/04/05 06:00
medline 2013/06/20 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Webb BT Webb Bradley T BT Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Guo AY Guo An-Yuan AY
Maher BS Maher Brion S BS
Zhao Z Zhao Zhongming Z
van den Oord EJ van den Oord Edwin J EJ
Kendler KS Kendler Kenneth S KS
Riley BP Riley Brien P BP
Gillespie NA Gillespie Nathan A NA
Prescott CA Prescott Carol A CA
Middeldorp CM Middeldorp Christel M CM
Willemsen G Willemsen Gonneke G
de Geus EJ de Geus Eco Jc EJ
Hottenga JJ Hottenga Jouke-Jan JJ
Boomsma DI Boomsma Dorret I DI
Slagboom EP Slagboom Eline P EP
Wray NR Wray Naomi R NR
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Wright MJ Wright Margie J MJ
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A PA
Gelernter J Gelernter Joel J
Knowles JA Knowles James A JA
Hamilton SP Hamilton Steven P SP
Weissman MM Weissman Myrna M MM
Fyer AJ Fyer Abby J AJ
Huezo-Diaz P Huezo-Diaz Patricia P
McGuffin P McGuffin Peter P
Farmer A Farmer Anne A
Craig IW Craig Ian W IW
Lewis C Lewis Cathryn C
Sham P Sham Pak P
Crowe RR Crowe Raymond R RR
Flint J Flint Jonathan J
Hettema JM Hettema John M JM
INVESTIGATORS
JOURNAL
VOLUME: 20
ISSUE: 10
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2012
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5438
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
K05 AA017688 NIAAA NIH HHS United States
R01 AA011408 NIAAA NIH HHS United States
R21 MH079192 NIMH NIH HHS United States
R21MH79192 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Anxiety Disorders genetics
Genetic Linkage genetics
Genome, Human genetics
Humans genetics
Phenotype genetics
SUPPLEMENTARY MESH
SUPPLMESHNAME SUPPLMESHTYPE
Neuroticism Disease
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3449070 NLM