title: Genomewide scan in families with schizophrenia from the founder population of Afrikaners reveals evidence for linkage and uniparental disomy on chromosome 1.
abstract: We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of.012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners.
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Burt
authors.forename: Diana
authors.initials: D
authors.lastname: Hall
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bochum
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: S Laura
authors.initials: SL
authors.lastname: Lundy
authors.forename: Marie
authors.initials: M
authors.lastname: Torrington
authors.forename: J Louw
authors.initials: JL
authors.lastname: Roos
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
mesh_terms: D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D012559:Schizophrenia / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D018709:Statistics, Nonparametric; D024182:Uniparental Disomy; D044465:White People / Q000235:genetics