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Article: Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships
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TitleGenome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships
 
AuthorsNash, MW3
HuezoDiaz, P3
Williamson, RJ3
Sterne, A3
Purcell, S2 3
Hoda, F3
Cherny, SS6
Abecasis, G5
Prince, M1
Gray, JA1
Ball, D3
Asherson, P3
Mann, A1
Goldberg, D1
McGuffin, P3
Farmer, A3
Plomin, R3
Craig, IW3
Sham, PC3 4
 
Issue Date2004
 
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
CitationHuman Molecular Genetics, 2004, v. 13 n. 19, p. 2173-2182 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddh239
 
AbstractThere is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34 371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller - but statistically powerful - sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects. © Oxford University Press 2004; all rights reserved.
 
ISSN0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
DOIhttp://dx.doi.org/10.1093/hmg/ddh239
 
ISI Accession Number IDWOS:000223941500002
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorNash, MW
 
dc.contributor.authorHuezoDiaz, P
 
dc.contributor.authorWilliamson, RJ
 
dc.contributor.authorSterne, A
 
dc.contributor.authorPurcell, S
 
dc.contributor.authorHoda, F
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorAbecasis, G
 
dc.contributor.authorPrince, M
 
dc.contributor.authorGray, JA
 
dc.contributor.authorBall, D
 
dc.contributor.authorAsherson, P
 
dc.contributor.authorMann, A
 
dc.contributor.authorGoldberg, D
 
dc.contributor.authorMcGuffin, P
 
dc.contributor.authorFarmer, A
 
dc.contributor.authorPlomin, R
 
dc.contributor.authorCraig, IW
 
dc.contributor.authorSham, PC
 
dc.date.accessioned2011-12-16T08:09:19Z
 
dc.date.available2011-12-16T08:09:19Z
 
dc.date.issued2004
 
dc.description.abstractThere is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34 371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller - but statistically powerful - sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects. © Oxford University Press 2004; all rights reserved.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationHuman Molecular Genetics, 2004, v. 13 n. 19, p. 2173-2182 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddh239
 
dc.identifier.citeulike3037303
 
dc.identifier.doihttp://dx.doi.org/10.1093/hmg/ddh239
 
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dc.identifier.isiWOS:000223941500002
 
dc.identifier.issn0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
dc.identifier.issue19
 
dc.identifier.pmid15351774
 
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dc.identifier.spage2173
 
dc.identifier.urihttp://hdl.handle.net/10722/143669
 
dc.identifier.volume13
 
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHuman Molecular Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.titleGenome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships
 
dc.typeArticle
 
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Author Affiliations
  1. King's College London
  2. Whitehead Institute for Biomedical Research
  3. Medical Research Council
  4. The University of Hong Kong
  5. University Michigan Ann Arbor
  6. Wellcome Trust Centre for Human Genetics