1. ¹Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland
2. ²Department of Medical Genetics, University of Helsinki, Biomedicum, Helsinki, Finland
3. ³Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki, Finland
4. ⁴Department of Adolescent Psychiatry, Jorvi Hospital, Espoo, Finland
5. ⁵Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
6. ⁶Program in Medical and Population Genetics, The Broad Institute, MIT and Harvard University, Cambridge, MA, USA

Correspondence: Dr L Peltonen, Department of Molecular Medicine, National Public Health Institution, Biomedicum, Haartmaninkatu 8, Helsinki 00251, Finland. E-mail: leena.peltonen@ktl.fi

Received 6 February 2007; Revised 29 March 2007; Accepted 7 May 2007; Published online 19 June 2007.

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.