title: A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12.
abstract: Suicidal behavior is commonly associated with depression. Twin studies indicate that both suicidality and major depressive disorder (MDD) are heritable. However, epidemiological evidence suggests that the inheritance of suicidality is likely to be independent of the underlying psychiatric disorder, implying a distinct genetic contribution to suicidality. We conducted a genomewide linkage search aiming to detect genomic loci that may harbor susceptibility genes contributing to risk for suicidality in recurrent MDD. Affected sibling pair (ASP) variance components analysis was performed using the Depression Network cohort of 971 ASPs. The quantitative trait measuring suicidality as a broad phenotype, encompassing ideation and suicide attempts, was established from Schedules for Clinical Assessment in Neuropsychiatry interview items. We examined 1,060 genotyped microsatellite markers with an average spacing of 3.3 cM. Empirical thresholds for linkage evidence were set by whole-genome simulations (LOD = 2.71 for genomewide significance, 1.71 for suggestive linkage). No genomewide significant findings were found. Marker D3S1234 on 3p14 achieved suggestive linkage and yielded a maximum LOD of 1.853 (P = 0.0017), loci 9p24.3 and 18q22-q23 achieved LOD scores >1.5. We found some support for linkage to 2p12 (LOD = 1.2, P = 0.0087) which was previously implicated in linkage studies of suicidality. Our follow-up meta-analysis of five studies showed strong linkage to this region (P = 2 × 10(-6) ). In conclusion, this study analyzed suicidality as a continuous trait in MDD. We found modest evidence for linkage on 3p14. Our meta-analysis supports previous evidence of linkage to suicidality on 2p12. Some candidate genes in these regions may plausibly be implicated in suicidality. © 2010 Wiley-Liss, Inc.
authors.affiliation: MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Butler
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
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 T
authors.initials: LT
authors.lastname: Middleton
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Julia
authors.initials: J
authors.lastname: Perry
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
mesh_terms: D000328:Adult; D017668:Age of Onset; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D035781:Siblings; D059020:Suicidal Ideation; D013406:Suicide, Attempted
chemical_list: D005819:Genetic Markers