title: A genome-wide search for schizophrenia susceptibility genes.
abstract: We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0-31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication.
authors.affiliation: Axys Pharmaceuticals, La Jolla, California, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Shaw
authors.forename: M
authors.initials: M
authors.lastname: Kelly
authors.forename: A B
authors.initials: AB
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Shields
authors.forename: P J
authors.initials: PJ
authors.lastname: Hopkins
authors.forename: J
authors.initials: J
authors.lastname: Loftus
authors.forename: S H
authors.initials: SH
authors.lastname: Laval
authors.forename: A
authors.initials: A
authors.lastname: Vita
authors.forename: M
authors.initials: M
authors.lastname: De Hert
authors.forename: L R
authors.initials: LR
authors.lastname: Cardon
authors.forename: T J
authors.initials: TJ
authors.lastname: Crow
authors.forename: R
authors.initials: R
authors.lastname: Sherrington
authors.forename: L E
authors.initials: LE
authors.lastname: DeLisi
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D005819:Genetic Markers