Genomewide scan in families with schizophrenia from the founder population of Afrikaners reveals evidence for linkage and uniparental disomy on chromosome 1.
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.
Abecasis
Gonçalo R
GR
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Burt
Rachel A
RA
Hall
Diana
D
Bochum
Sylvia
S
Doheny
Kimberly F
KF
Lundy
S Laura
SL
Torrington
Marie
M
Roos
J Louw
JL
Gogos
Joseph A
JA
Karayiorgou
Maria
M
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