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

Breen, Gerome and Webb, Bradley Todd and Butler, Amy W. and van den Oord, Edwin J. C. G. and Tozzi, Federica and Craddock, Nick and Gill, Mike and Korszun, Ania and Maier, Wolfgang and Middleton, Lefkos and Mors, Ole and Owen, Michael J. and Cohen-Woods, Sarah and Perry, Julia and Galwey, Nicholas W. and Upmanyu, Ruchi and Craig, Ian and Lewis, Cathryn M. and Ng, Mandy and Brewster, Shyama and Preisig, Martin and Rietschel, Marcella and Jones, Lisa and Knight, Jo and Rice, John and Muglia, Pierandrea and Farmer, Anne E. and McGuffin, Peter (2011) A genome-wide significant linkage for severe depression on chromosome 3:the depression network study. American Journal of Psychiatry, 168 (8). pp. 840-847. ISSN 0002-953X

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OBJECTIVE: 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.

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Journal Article
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American Journal of Psychiatry
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07 Jun 2016 13:18
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22 Nov 2022 03:21