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
18519823
TITLE
Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
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 NlmCategory: OBJECTIVE
To undertake a comprehensive genome-wide 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 NlmCategory: METHODS
Genome-wide linkage scan.
SETTING NlmCategory: METHODS
Twin individuals and their family members from Australia and the Netherlands.
PARTICIPANTS NlmCategory: METHODS
Nineteen thousand six hundred thirty-five 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
DATE PUBLISHED
2008 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2008/06/04 09:00
medline 2008/06/18 09:00
entrez 2008/06/04 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wray NR Wray Naomi R NR Department of Genetic Epidemiology, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane, Australia 4029. naomi.wray@qimr.edu.au
Middeldorp CM Middeldorp Christel M CM
Birley AJ Birley Andrew J AJ
Gordon SD Gordon Scott D SD
Sullivan PF Sullivan Patrick F PF
Visscher PM Visscher Peter M PM
Nyholt DR Nyholt Dale R DR
Willemsen G Willemsen Gonneke G
de Geus EJ de Geus Eco J C EJ
Slagboom PE Slagboom P Eline PE
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Boomsma DI Boomsma Dorret I DI
INVESTIGATORS
JOURNAL
VOLUME: 65
ISSUE: 6
TITLE: Archives of general psychiatry
ISOABBREVIATION: Arch. Gen. Psychiatry
YEAR: 2008
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1538-3636
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Arch Gen Psychiatry
COUNTRY: United States
ISSNLINKING: 0003-990X
NLMUNIQUEID: 0372435
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
MH59160 NIMH NIH HHS United States
R01 HL55976 NHLBI NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Australia
Chromosome Mapping
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 18
Cohort Studies
Comorbidity
Cross-Cultural Comparison
Diseases in Twins psychology
Female psychology
Genotype psychology
Humans psychology
Lod Score psychology
Longitudinal Studies psychology
Male psychology
Netherlands psychology
Neurotic Disorders psychology
Personality Disorders psychology
Personality Inventory psychology
Sex Factors psychology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS544183 NLM
PMC3912824 NLM
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