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.

Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11

“…[16][17][18] There is also suggestive evidence for linkage of both schizophrenia and bipolar disorder to chromosome 22q (reviewed in Karayiourgou and Gogos 19 ; see also [20][21][22][23] ). Early studies on biochemical markers for schizophrenia reported higher COMT activity in patients compared to controls (reviewed in Baron et al 24 ), but these results were not conclusive.…”

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

“…Lindholm et al 14 reported, in one very large SZ pedigree of Sweden, a lod score of 6.6 in 6q25.2 and described a 6 cM haplotype in this region segregating with the disorder. However, we 15 and others, [16][17][18][19][20][21][22] as well as a meta-analysis, 23 reported negative results in 1q21-q22, whereas two studies 24,25 provided confirmations.…”

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).…”