title: Association of DISC1 with autism and Asperger syndrome.
abstract: The DISC1 gene at 1q42 has generated considerable interest in various psychiatric diseases, since a balanced translocation interrupting the gene was found to cosegregate with schizophrenia and related mental illnesses in a large Scottish pedigree. To date, linkage and association findings to this locus have been replicated in several study samples ascertained for psychotic disorders. However, the biological function of DISC1 in neuronal development would suggest a potential role for this gene also in other, early onset neuropsychiatric disorders. Here we have addressed the allelic diversity of the DISC1, DISC2 and TRAX genes, clustered in 1q42, in Finnish families ascertained for infantile autism (97 families, n(affected)=138) and Asperger syndrome (29 families, n(affected)=143). We established association between autism and a DISC1 intragenic microsatellite (D1S2709; P=0.004). In addition, evidence for association to Asperger syndrome was observed with an intragenic single nucleotide polymorphism (SNP) of DISC1 (rs1322784; P=0.0058), as well as with a three-SNP haplotype (P=0.0013) overlapping the HEP3 haplotype, that was previously observed to associate with schizophrenia in Finnish families. The strongest associations were obtained with broad diagnostic categories for both disorders and with affected males only, in agreement with the previous sex-dependent effects reported for DISC1. These results would further support the involvement of DISC1 gene also in the etiopathogenesis of early onset neuropsychiatric disorders.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Kilpinen
authors.forename: T
authors.initials: T
authors.lastname: Ylisaukko-Oja
authors.forename: W
authors.initials: W
authors.lastname: Hennah
authors.forename: O M
authors.initials: OM
authors.lastname: Palo
authors.forename: T
authors.initials: T
authors.lastname: Varilo
authors.forename: R
authors.initials: R
authors.lastname: Vanhala
authors.forename: T
authors.initials: T
authors.lastname: Nieminen-von Wendt
authors.forename: L
authors.initials: L
authors.lastname: von Wendt
authors.forename: T
authors.initials: T
authors.lastname: Paunio
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D020817:Asperger Syndrome / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005192:Family Health; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
chemical_list: C412476:DISC1 protein, human; C448722:DISC2 gene product, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C498305:TSNAX protein, human