Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes.
Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and "affected only" models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the "affected only" recessive model (ZMAX = 2.35; theta M = theta F); allowing for a constant sex difference in recombination fractions found in reference pedigrees, ZMAX = 2.78 (theta M/theta F = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ("affected only" dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia.
Pulver
A E
AE
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Lasseter
V K
VK
Kasch
L
L
Wolyniec
P
P
Nestadt
G
G
Blouin
J L
JL
Kimberland
M
M
Babb
R
R
Vourlis
S
S
Chen
H
H
D015415:Biomarkers; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002898:Chromosomes, Human, Pair 8; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D012559:Schizophrenia / Q000235:genetics*
D015415:Biomarkers