title: Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population.
abstract: The long-standing concept that schizophrenia (SC) and bipolar disorder (BP) represent two distinct illnesses has been recently challenged by findings of overlap of genetic susceptibility loci for these two diseases. We report here the results of a linkage disequilibrium (LD) analysis of chromosome 18 utilizing subjects with SC from the Central Valley of Costa Rica. Evidence of association (P < 0.05) was obtained in three chromosomal regions: 18p11.31 (D18S63), 18q12.3 (D18S474), and 18q22.3-qter (D18S1161, D18S70), all of which overlap or are in close proximity with loci previously shown to be in LD with BP, type I in this population. Since both the SC and bipolar samples contained cases with a history of mania and almost all cases of SC and BP had a history of psychosis, we performed an alternative phenotyping strategy to determine whether presence or absence of mania, in the context of psychosis, would yield distinct linkage patterns along chromosome 18. To address this issue, a cohort of psychotic patients (including a range of DSMIV diagnoses) was divided into two groups based on the presence or absence of mania. Regions that showed association with SC showed segregation of association when the sample was stratified by history of mania. Our results are compared with previous genetic studies of susceptibility to SC or BP, in Costa Rica as well as in other populations. This study illustrates the importance of detailed phenotype analysis in the search for susceptibility genes influencing complex psychiatric disorders in isolated populations and suggests that subdivision of psychoses by presence or absence of past mania syndromes may be useful to define genetic subtypes of chronic psychotic illness.
authors.affiliation: Psychiatric Genetics Research Center, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Walss-Bass
authors.forename: Michael A
authors.initials: MA
authors.lastname: Escamilla
authors.forename: Henriette
authors.initials: H
authors.lastname: Raventos
authors.forename: A Patricia
authors.initials: AP
authors.lastname: Montero
authors.forename: Regina
authors.initials: R
authors.lastname: Armas
authors.forename: Albana
authors.initials: A
authors.lastname: Dassori
authors.forename: Salvador
authors.initials: S
authors.lastname: Contreras
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Rolando
authors.initials: R
authors.lastname: Medina
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Balderas
authors.forename: Douglas
authors.initials: D
authors.lastname: Levinson
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Pereira
authors.forename: Mariana
authors.initials: M
authors.lastname: Pereira
authors.forename: Ivannia
authors.initials: I
authors.lastname: Atmella
authors.forename: Lisa
authors.initials: L
authors.lastname: Nesmith
authors.forename: Robin
authors.initials: R
authors.lastname: Leach
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D003364:Costa Rica; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*