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  • Original Article
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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, naffected=138) and Asperger syndrome (29 families, naffected=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.

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Acknowledgements

Elli Kempas is acknowledged for her advice in issues concerning the DNA samples and microsatellite genotyping. Anu-Maria Loukola and Kaisa Silander are acknowledged for their technical support in SNP genotyping with Sequenom. We would also thank Drs Irma Järvelä, Reija Alen, Raili Riikonen and Ismo Makkonen for their contribution in collecting and characterizing the study samples. TY is supported by the Cure Autism Now grant and WH by the Finnish Cultural Foundation, Aili and Paul Pennanen and Piippa-Stiina Immonen Grants. The study has been supported by the Center of Excellence of the Academy of Finland, Biocentrum Helsinki, Finland and the Päivikki and Sakari Sohlberg Foundation.

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Kilpinen, H., Ylisaukko-oja, T., Hennah, W. et al. Association of DISC1 with autism and Asperger syndrome. Mol Psychiatry 13, 187–196 (2008). https://doi.org/10.1038/sj.mp.4002031

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