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.
  
  
  METHODS
  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.
authors.affiliation: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London.
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Bradley Todd
authors.initials: BT
authors.lastname: Webb
authors.forename: Amy W
authors.initials: AW
authors.lastname: Butler
authors.forename: Edwin J C G
authors.initials: EJ
authors.lastname: van den Oord
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Mike
authors.initials: M
authors.lastname: Gill
authors.forename: Ania
authors.initials: A
authors.lastname: Korszun
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Lefkos
authors.initials: L
authors.lastname: Middleton
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen-Woods
authors.forename: Julia
authors.initials: J
authors.lastname: Perry
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Galwey
authors.forename: Ruchi
authors.initials: R
authors.lastname: Upmanyu
authors.forename: Ian
authors.initials: I
authors.lastname: Craig
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Mandy
authors.initials: M
authors.lastname: Ng
authors.forename: Shyama
authors.initials: S
authors.lastname: Brewster
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.forename: John
authors.initials: J
authors.lastname: Rice
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012008:Recurrence; D012306:Risk; D035781:Siblings; D055815:Young Adult
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7