Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

Wray, Naomi R., Middeldorp, Christel M., Birley, Andrew J., Gordon, Scott D., Sullivan, Patrick F., Visscher, Peter M., Nyholt, Dale R, Willemsen, Gonneke, de Geus, Eco J.C., Slagboom, P. Eline, Montgomery, Grant W., Martin, Nicholas G. and Boomsma, Dorret I. (2008) Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands. Archives of General Psychiatry, 65 6: 649-658. doi:10.1001/archpsyc.65.6.649

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Author Wray, Naomi R.
Middeldorp, Christel M.
Birley, Andrew J.
Gordon, Scott D.
Sullivan, Patrick F.
Visscher, Peter M.
Nyholt, Dale R
Willemsen, Gonneke
de Geus, Eco J.C.
Slagboom, P. Eline
Montgomery, Grant W.
Martin, Nicholas G.
Boomsma, Dorret I.
Title Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands
Journal name Archives of General Psychiatry   Check publisher's open access policy
ISSN 2168-6238
Publication date 2008
Year available 2008
Sub-type Article (original research)
DOI 10.1001/archpsyc.65.6.649
Open Access Status File (Publisher version)
Volume 65
Issue 6
Start page 649
End page 658
Total pages 10
Place of publication Chicago, IL, United States
Publisher American Medical Association
Collection year 2008
Language eng
Formatted abstract
Context: People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders.

Objectives: To undertake a comprehensive genomewide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency.

Design: Genome-wide linkage scan.

Setting: Twin individuals and their family members from Australia and the Netherlands.

Participants: Nineteen thousand six hundred thirtyfive sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers.

Methods: Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results.

Results: Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice.

Conclusions: Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.
Keyword Personality traits
Onset major depression
Population based twin
Anxiety Disorders
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes For ERA

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 26 times in Scopus Article | Citations
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Created: Thu, 23 Oct 2014, 17:48:21 EST by Debra McMurtrie on behalf of Queensland Brain Institute