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

Webb, Bradley T., Guo, An-Yuan, Maher, Brion S., Zhao, Zhongming, van den Oord, Edwin J., Kendler, Kenneth S., Riley, Brien P., Gillespie, Nathan A., Prescott, Carol A., Middeldorp, Christel M., Willemsen, Gonneke, de Geus, Eco J. C., Hottenga, Jouke-Jan, Boomsma, Dorret I., Slagboom, Eline P., Wray, Naomi R., Montgomery, Grant W., Martin, Nicholas G., Wright, Margie J., Heath, Andrew C., Madden, Pamela A., Gelernter, Joel, Knowles, James A., Hamilton, Steven P., Weissman, Myrna M., Fyer, Abby J., Huezo-Diaz, Patricia, McGuffin, Peter, Farmer, Anne, Craig, Ian W., Lewis, Cathryn, Sham, Pak, Crowe, Raymond. R., Flint, Jonathan and Hettema, John M. (2012) Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes. European Journal of Human Genetics, 20 10: 1078-1084. doi:10.1038/ejhg.2012.47


Author Webb, Bradley T.
Guo, An-Yuan
Maher, Brion S.
Zhao, Zhongming
van den Oord, Edwin J.
Kendler, Kenneth S.
Riley, Brien P.
Gillespie, Nathan A.
Prescott, Carol A.
Middeldorp, Christel M.
Willemsen, Gonneke
de Geus, Eco J. C.
Hottenga, Jouke-Jan
Boomsma, Dorret I.
Slagboom, Eline P.
Wray, Naomi R.
Montgomery, Grant W.
Martin, Nicholas G.
Wright, Margie J.
Heath, Andrew C.
Madden, Pamela A.
Gelernter, Joel
Knowles, James A.
Hamilton, Steven P.
Weissman, Myrna M.
Fyer, Abby J.
Huezo-Diaz, Patricia
McGuffin, Peter
Farmer, Anne
Craig, Ian W.
Lewis, Cathryn
Sham, Pak
Crowe, Raymond. R.
Flint, Jonathan
Hettema, John M.
Title Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
1476-5438
Publication date 2012-04-04
Sub-type Article (original research)
DOI 10.1038/ejhg.2012.47
Open Access Status Other
Volume 20
Issue 10
Start page 1078
End page 1084
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing
Collection year 2013
Language eng
Formatted 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, PSR and POR, 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 PSRP-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.
Keyword Anxiety
Neuroticism
Panic disorder
Linkage
Metaanalysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication: 4 April 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
 
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Created: Fri, 13 Jul 2012, 00:18:37 EST by Debra McMurtrie on behalf of Queensland Brain Institute