A Single Nucleotide Polymorphism Fine Mapping Study of Chromosome 1q42.1 Reveals the Vulnerability Genes for Schizophrenia, GNPAT and DISC1: Association with Impairment of Sustained Attention
Journal
Biological Psychiatry
Journal Volume
60
Journal Volume
60
Journal Issue
6
Journal Issue
6
Pages
554-562
Start Page
554
End Page
562
ISSN
0006-3223
Date Issued
2006-09-15
Author(s)
Liu Y.-L.
Fann C.S.-J.
Wu J.-Y.
Hung S.-I.
Chen C.-H.
Jou Y.-S.
Liu S.-K.
Ouyang W.-C.
Chan H.-Y.
Chen J.-J.
Yang W.-C.
Lin C.-Y.
Lee S.F.C.
Abstract
Background: The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to search for the vulnerability genes of schizophrenia. Methods: We selected 120 SNPs covering 1 Mb around D1S251 from the public database. These selected SNPs were initially validated if allele frequency was >10%. Forty-seven validated SNPs were genotyped in 102 families with at least 2 siblings affected with schizophrenia. Results: Two SNP blocks showed significant association with schizophrenia. Block 1 (five-SNP), located between intron 2 and intron 13 of the glyceronephosphate O-acyltransferase (GNPAT) gene, showed the most significant associations using single-locus TDT (z = -2.07, p = .038, df = 1) and haplotype association analyses (z = -1.99, p = .046, df = 1). Block 2 (two-SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia 1 (DISC1) gene, also showed the most significant results in both the single-locus (z = -3.22, p = .0013, df = 1) and haplotype association analyses (z = 3.35, p = .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly in the patient group with sustained attention deficits as assessed by the Continuous Performance Test. Conclusions: Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia, and DISC1 is associated with sustained attention deficits. ? 2006 Society of Biological Psychiatry.
SDGs
Other Subjects
disrupted in schizophrenia 1 protein; gene product; glyceronephosphate o acyltransferase; protein; unclassified drug; article; attention disturbance; chromosome 1q; chromosome analysis; cognitive defect; controlled study; female; gene frequency; gene identification; gene locus; gene mapping; genetic association; genetic risk; genetic susceptibility; genotype; haplotype; human; intron; major clinical study; male; neuropsychological test; priority journal; protein determination; protein expression; schizophrenia; sibling; single nucleotide polymorphism; Acyltransferases; Attention; Chromosome Mapping; Chromosomes, Human, Pair 1; Family Health; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Linkage Disequilibrium; Male; Nerve Tissue Proteins; Neuropsychological Tests; Polymorphism, Single Nucleotide; Schizophrenia
Type
journal article