title: Association between a disrupted-in-schizophrenia 1 (DISC1) single nucleotide polymorphism and schizophrenia in a combined Scandinavian case-control sample.
abstract: Disrupted-in-schizophrenia-1 (DISC1), located on chromosome 1q42.1, is linked to rare familial schizophrenia in a large Scottish family. The chromosomal translocation that segregates with the disease results in a truncated protein that impairs neurite outgrowth and proper development of the cerebral cortex, suggesting that lost DISC1 function may underlie neurodevelopmental dysfunction in schizophrenia. DISC1 has been associated with schizophrenia in multiple populations, but there is little evidence of convergence across populations. In the present case-control study three Scandinavian samples of 837 individuals affected with schizophrenia and 1473 controls, were used in an attempt to replicate previously reported associations between single nucleotide polymorphisms (SNPs) in DISC1 and schizophrenia. No SNP with allele frequency above 10% was significantly associated with the disease after correction for multiple testing. However, the minor allele of rs3737597 (frequency 2%) in the 3'-untranslated region (UTR), previously identified as a risk allele in Finnish families, was significantly and consistently associated with the disorder across the three samples, (p-value corrected for multiple testing was 0.002). Our results suggest that a relatively uncommon DISC1 mutation, which increases the susceptibility for schizophrenia may be segregating in the Scandinavian population, and support the view that common DISC1 SNP alleles are unlikely to account for a substantial proportion of the genetic risk of the disease across populations of European descent.
authors.affiliation: Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden. peter.saetre@ki.se
authors.forename: Peter
authors.initials: P
authors.lastname: Saetre
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.forename: Alessandra
authors.initials: A
authors.lastname: De Franciscis
authors.forename: Per
authors.initials: P
authors.lastname: Lundmark
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Anna
authors.initials: A
authors.lastname: Kähler
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Jakobsen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Håkan
authors.initials: H
authors.lastname: Hall
authors.forename: Lars
authors.initials: L
authors.lastname: Terenius
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries / Q000208:ethnology; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins