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

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A genome-wide significant linkage for severe depression on chromosome 3: the depression network study. / Breen, Gerome; Webb, Bradley Todd; Butler, Amy W. et al.
In: American Journal of Psychiatry, Vol. 168, No. 8, 08.2011, p. 840-847.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Breen, G, Webb, BT, Butler, AW, van den Oord, EJCG, Tozzi, F, Craddock, N, Gill, M, Korszun, A, Maier, W, Middleton, L, Mors, O, Owen, MJ, Cohen-Woods, S, Perry, J, Galwey, NW, Upmanyu, R, Craig, I, Lewis, CM, Ng, M, Brewster, S, Preisig, M, Rietschel, M, Jones, L, Knight, J, Rice, J, Muglia, P, Farmer, AE & McGuffin, P 2011, 'A genome-wide significant linkage for severe depression on chromosome 3: the depression network study', American Journal of Psychiatry, vol. 168, no. 8, pp. 840-847. https://doi.org/10.1176/appi.ajp.2011.10091342

APA

Breen, G., Webb, B. T., Butler, A. W., van den Oord, E. J. C. G., Tozzi, F., Craddock, N., Gill, M., Korszun, A., Maier, W., Middleton, L., Mors, O., Owen, M. J., Cohen-Woods, S., Perry, J., Galwey, N. W., Upmanyu, R., Craig, I., Lewis, C. M., Ng, M., ... McGuffin, P. (2011). A genome-wide significant linkage for severe depression on chromosome 3: the depression network study. American Journal of Psychiatry, 168(8), 840-847. https://doi.org/10.1176/appi.ajp.2011.10091342

Vancouver

Breen G, Webb BT, Butler AW, van den Oord EJCG, Tozzi F, Craddock N et al. A genome-wide significant linkage for severe depression on chromosome 3: the depression network study. American Journal of Psychiatry. 2011 Aug;168(8):840-847. doi: 10.1176/appi.ajp.2011.10091342

Author

Breen, Gerome ; Webb, Bradley Todd ; Butler, Amy W. et al. / A genome-wide significant linkage for severe depression on chromosome 3 : the depression network study. In: American Journal of Psychiatry. 2011 ; Vol. 168, No. 8. pp. 840-847.

Bibtex

@article{b7c44e67817c4c58af07821285b9db1a,
title = "A genome-wide significant linkage for severe depression on chromosome 3: the depression network study",
abstract = "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.",
keywords = "Adult, Age of Onset, Aged, Alleles, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 7, Depressive Disorder, Major, Female, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lod Score, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Receptors, Metabotropic Glutamate, Recurrence, Risk, Siblings, Young Adult",
author = "Gerome Breen and Webb, {Bradley Todd} and Butler, {Amy W.} and {van den Oord}, {Edwin J. C. G.} and Federica Tozzi and Nick Craddock and Mike Gill and Ania Korszun and Wolfgang Maier and Lefkos Middleton and Ole Mors and Owen, {Michael J.} and Sarah Cohen-Woods and Julia Perry and Galwey, {Nicholas W.} and Ruchi Upmanyu and Ian Craig and Lewis, {Cathryn M.} and Mandy Ng and Shyama Brewster and Martin Preisig and Marcella Rietschel and Lisa Jones and Jo Knight and John Rice and Pierandrea Muglia and Farmer, {Anne E.} and Peter McGuffin",
year = "2011",
month = aug,
doi = "10.1176/appi.ajp.2011.10091342",
language = "English",
volume = "168",
pages = "840--847",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "8",

}

RIS

TY - JOUR

T1 - A genome-wide significant linkage for severe depression on chromosome 3

T2 - the depression network study

AU - Breen, Gerome

AU - Webb, Bradley Todd

AU - Butler, Amy W.

AU - van den Oord, Edwin J. C. G.

AU - Tozzi, Federica

AU - Craddock, Nick

AU - Gill, Mike

AU - Korszun, Ania

AU - Maier, Wolfgang

AU - Middleton, Lefkos

AU - Mors, Ole

AU - Owen, Michael J.

AU - Cohen-Woods, Sarah

AU - Perry, Julia

AU - Galwey, Nicholas W.

AU - Upmanyu, Ruchi

AU - Craig, Ian

AU - Lewis, Cathryn M.

AU - Ng, Mandy

AU - Brewster, Shyama

AU - Preisig, Martin

AU - Rietschel, Marcella

AU - Jones, Lisa

AU - Knight, Jo

AU - Rice, John

AU - Muglia, Pierandrea

AU - Farmer, Anne E.

AU - McGuffin, Peter

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Adult

KW - Age of Onset

KW - Aged

KW - Alleles

KW - Chromosomes, Human, Pair 3

KW - Chromosomes, Human, Pair 7

KW - Depressive Disorder, Major

KW - Female

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Lod Score

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Receptors, Metabotropic Glutamate

KW - Recurrence

KW - Risk

KW - Siblings

KW - Young Adult

U2 - 10.1176/appi.ajp.2011.10091342

DO - 10.1176/appi.ajp.2011.10091342

M3 - Journal article

C2 - 21572164

VL - 168

SP - 840

EP - 847

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 8

ER -