title: Genome scan in sibling pairs with juvenile-onset mood disorders: Evidence for linkage to 13q and Xq.
abstract: Mood disorders (bipolar and depressive disorders) in children and adolescents are associated with significant morbidity and mortality. Twin and family studies, for the most part, indicate higher familiality and heritability for mood disorders that onset in childhood/adolescence than those that onset in adulthood. To identify the genetic contribution to mood disorders that onset in childhood/adolescence, we performed a genome scan on 146 nuclear families from Hungary containing an affected proband and affected siblings. In total, the pedigrees contained 303 affected children: 146 probands, 137 siblings with a first episode of mood disorder before 14.9 years of age, and 20 siblings with onset of their first episode after 14.9 years of age but before the age of 18. The results of the genome scan using 405 microsatellite markers did not provide evidence for linkage at the recommended genome wide significance level for any novel loci. However, markers on two chromosomes, 13q and Xq, provided evidence for linkage in regions previously identified as linked to bipolar disorder in multiple studies. For the marker on chromosome 13q the peak non-parametric multipoint LOD score was at the marker D13S779 (LOD = 1.5, P = 0.004). On chromosome Xq, evidence for linkage was observed across a large region spanning two regions previously linked to bipolar disorder; Xq24 to Xq28, with a peak at marker TTTA062 (LOD 2.10, P = 0.0009) in Xq28. Results for these regions exceed the recommended P-value for a replication study of P < 0.01 and thus provide evidence for these two loci as contributing to mood disorders with juvenile onset.
authors.affiliation: Toronto Western Research Institute, University Health Network, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Wigg
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Lissette
authors.initials: L
authors.lastname: Gomez
authors.forename: Eniko
authors.initials: E
authors.lastname: Kiss
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kapornai
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Tamás
authors.forename: László
authors.initials: L
authors.lastname: Mayer
authors.forename: Ildikó
authors.initials: I
authors.lastname: Baji
authors.forename: Gabriella
authors.initials: G
authors.lastname: Daróczi
authors.forename: István
authors.initials: I
authors.lastname: Benák
authors.forename: Viola Kothencné
authors.initials: VK
authors.lastname: Osváth
authors.forename: Edit
authors.initials: E
authors.lastname: Dombovári
authors.forename: Emília
authors.initials: E
authors.lastname: Kaczvinszk
authors.forename: Márta
authors.initials: M
authors.lastname: Besnyõ
authors.forename: Julia
authors.initials: J
authors.lastname: Gádoros
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Judit
authors.initials: J
authors.lastname: Székely
authors.forename: Maria
authors.initials: M
authors.lastname: Kovacs
authors.forename: Agnes
authors.initials: A
authors.lastname: Vetró
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics*; D035781:Siblings