A genome-wide significant linkage for severe depression on chromosome 3: the depression network study

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dc.contributor.authorBreen, G.
dc.contributor.authorWebb, B.
dc.contributor.authorButler, A.
dc.contributor.authorvan den Oord, E.
dc.contributor.authorTozzi, F.
dc.contributor.authorCraddock, N.
dc.contributor.authorGill, M.
dc.contributor.authorKorszun, A.
dc.contributor.authorMaier, W.
dc.contributor.authorMiddleton, L.
dc.contributor.authorMors, O.
dc.contributor.authorOwen, M.
dc.contributor.authorCohen-Woods, S.
dc.contributor.authorPerry, J.
dc.contributor.authorGalwey, N.
dc.contributor.authorUpmanyu, R.
dc.contributor.authorCraig, I.
dc.contributor.authorLewis, C.
dc.contributor.authorNg, M.
dc.contributor.authorBrewster, S.
dc.contributor.authoret al.
dc.date.issued2011
dc.description.abstractOBJECTIVE: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. METHOD: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. RESULTS: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. CONCLUSIONS: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.
dc.description.statementofresponsibilityGerome Breen... Sarah Cohen-Woods... et al.
dc.identifier.citationAmerican Journal of Psychiatry, 2011; 168(8):840-847
dc.identifier.doi10.1176/appi.ajp.2011.10091342
dc.identifier.issn0002-953X
dc.identifier.issn1535-7228
dc.identifier.orcidCohen-Woods, S. [0000-0003-2199-6129]
dc.identifier.urihttp://hdl.handle.net/2440/76795
dc.language.isoen
dc.publisherAmer Psychiatric Press Inc
dc.rightsCopyright © American Psychiatric Association
dc.source.urihttps://doi.org/10.1176/appi.ajp.2011.10091342
dc.subjectChromosomes, Human, Pair 3
dc.subjectChromosomes, Human, Pair 7
dc.subjectHumans
dc.subjectGenetic Predisposition to Disease
dc.subjectRecurrence
dc.subjectReceptors, Metabotropic Glutamate
dc.subjectRisk
dc.subjectSiblings
dc.subjectDepressive Disorder, Major
dc.subjectAge of Onset
dc.subjectGenotype
dc.subjectLod Score
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectYoung Adult
dc.subjectGenetic Linkage
dc.titleA genome-wide significant linkage for severe depression on chromosome 3: the depression network study
dc.typeJournal article
pubs.publication-statusPublished

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