title: Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.
abstract: To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals. To localize risk variants to genomic regions, we evaluated long-shared haplotypes, ≥10 Mb, identifying clusters of affected individuals who share such haplotypes. This extensive sharing, typically identical by descent, was significantly greater in cases than population controls, even after controlling for relatedness. Several regions of the genome exhibited substantial excess of shared haplotypes for affected individuals, including 3p21, 3p12, 4q28, and 5q23-q31. Two of these regions, 4q28 and 5q23-q31, showed significant linkage by traditional LOD score analysis and could harbor variants of more sizeable risk for psychosis or a multiplicity of risk variants. The pattern of haplotype sharing in 4q28 highlightsPCDH10, encoding a cadherin-related neuronal receptor, as possibly involved in risk.
authors.affiliation: Department of Statistics, Carnegie Mellon University, Pittsburgh, Pa, USA.
authors.forename: Corneliu A
authors.initials: CA
authors.lastname: Bodea
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, N.Y, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Melhem
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, Pa., USA.
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA.
authors.forename: Youeun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Palau Ministry of Health, Koror, Republic of Palau, USA.
authors.forename: Josepha
authors.initials: J
authors.lastname: Tiobech
authors.affiliation: Palau Ministry of Health, Koror, Republic of Palau, USA.
authors.forename: Pearl
authors.initials: P
authors.lastname: Marumoto
authors.affiliation: Palau Ministry of Health, Koror, Republic of Palau, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Yano
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, N.Y, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Department of Statistics, Carnegie Mellon University, Pittsburgh, Pa, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
authors.affiliation: University of Washington School of Public Health, Seattle, Wash, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Myles-Worsley
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA.
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.affiliation: Department of Psychiatry, University of California San Francisco, San Francisco, Calif., USA.
authors.forename: William
authors.initials: W
authors.lastname: Byerley
keywords: Genetics; Linkage analysis; Pedigree; Penetrance; Psychosis; Schizophrenia