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A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands

Abstract

The involvement of genetic factors in the etiology of autism has been clearly established. We undertook a genome-wide search for regions containing susceptibility genes for autism in 12 subjects with childhood autism and related pervasive developmental disorders (PDDs) and 44 controls from the relatively isolated population of the Faroe Islands. In total, 601 microsatellite markers distributed throughout the human genome with an average distance of 5.80 cM were genotyped, including 502 markers in the initial scan. The Faroese population structure and genetic relatedness of cases and controls were also evaluated. Based on a combined approach, including an assumption-free test as implemented in CLUMP, Fisher's exact test for specific alleles and haplotypes, and IBD0 probability calculations, we found association between autism and microsatellite markers in regions on 2q, 3p, 6q, 15q, 16p, and 18q. The most significant finding was on 3p25.3 (PT1=0.00003 and PT4=0.00007), which was also supported by other genetic studies. Furthermore, no evidence of population substructure was found, and a higher degree of relatedness among cases could not be detected, decreasing the risk of inflated P-values. Our data suggest that markers in these regions are in linkage disequilibrium with genes involved in the etiology of autism, and we hypothesize susceptibility genes for autism and related PDDs to be localized within these regions.

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Acknowledgements

We thank The Faroese association for autism, and the late chairman Mrs ‘Margrethe Joensen-Næs for their participation in this study. We also thank psychologist Lennart Pedersen, National Centre for Autism, Copenhagen, for diagnostic assessments, statistician Leslie Foldager, Centre for Basic Psychiatric Research, Aarhus University Hospital, Aarhus, for statistical advice, and research assistant Agata El Daoud for help with the genotyping. In addition, we thank assistant professors Thomas Bataillon and Roald Forsberg, The Bioinformatics Research Centre (BiRC), University of Aarhus and associate professor Jes Søe Petersen, Department of Population Biology, University of Copenhagen, for discussion of population genetics issues. This work was supported by The Danish Medical Research Council (Grant Number 9601887); The Lundbeck Foundation (Grants Numbers 39/98 and 59/99); Puljen til Styrkelse af Psykiatrisk Forskning i Aarhus Amt; Psykiatrisk forsknings fond; Ministry of Education, Culture and Research, The Faroese Government; Research Fund of the Faroese Savings Bank, Torshavn, Faroe Islands; Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands and Greenland.

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Lauritsen, M., Als, T., Dahl, H. et al. A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands. Mol Psychiatry 11, 37–46 (2006). https://doi.org/10.1038/sj.mp.4001754

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