Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

Abstract

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.

The ups and downs of Wnt signaling in prevalent neurological disorders

“…The human FZD3 gene is located on chromosome 8p21, a linkage locus containing a putative gene for schizophrenia (Pulver et al, 1995;Blouin et al, 1998;Kendler et al, 2000;Gurling et al, 2001). Candidate gene association studies in this region have shown that SNPs within the FZD3 gene are strongly associated with schizophrenia in Chinese Han (Yang et al, 2003;Zhang et al, 2004), as well as in Japanese descents (Katsu et al, 2003).…”

Association of Neuregulin 1 with schizophrenia and bipolar disorder in a second cohort from the Scottish population

“…7,[12][13][14][15][16][17][18][19][20][21][22] Fine mapping and haplotype analysis of the linkage peak in an Icelandic sample identified a haplotype, shared by seven out of the thirty-three families tested, implicating an B600 kb region. 7 A core haplotype from this region (Hap ICE ) spanning 290 kb and consisting of five singlenucleotide polymorphisms (SNPs) and two microsatellite markers was found to be over-represented in affected individuals (P = 0.000087, one-tailed; Figure 1).…”

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

“…8 In total, 17 complete or nearly complete genome scans for schizophrenia have now been published. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] None of these scans have revealed large single-gene effects. Concordance rates for schizophrenia in monozygotic twins are far short of 100% stressing the importance of environmental factors.…”