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Search for autism loci by combined analysis of Autism Genetic Resource Exchange and Finnish families

Authors

  • Tero Ylisaukko-oja MSc,

    1. Department of Molecular Medicine, National Public Health Institute, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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  • Maricela Alarcón PhD,

    1. Center for Neurobehavioral Genetics and Neuropsychiatric Research Institute, University of California, Los Angeles, CA
    2. Program in Neurogenetics, University of California, Los Angeles, CA
    3. Department of Neurology, University of California, Los Angeles, CA
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  • Rita M. Cantor PhD,

    1. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA
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  • Mari Auranen MD, PhD,

    1. Department of Molecular Medicine, National Public Health Institute, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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  • Raija Vanhala MD, PhD,

    1. Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
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  • Elli Kempas MLT,

    1. Department of Molecular Medicine, National Public Health Institute, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
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  • Lennart von Wendt MD, PhD,

    1. Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
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  • Irma Järvelä MD, PhD,

    1. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    2. Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki, Finland
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  • Daniel H. Geschwind MD, PhD,

    1. Center for Neurobehavioral Genetics and Neuropsychiatric Research Institute, University of California, Los Angeles, CA
    2. Program in Neurogenetics, University of California, Los Angeles, CA
    3. Department of Neurology, University of California, Los Angeles, CA
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  • Leena Peltonen MD, PhD

    Corresponding author
    1. Department of Molecular Medicine, National Public Health Institute, University of Helsinki, Helsinki, Finland
    • National Public Health Institute, Department of Molecular Medicine, Biomedicum, P.O. Box 104, 00251 Helsinki, Finland
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  • Members of the AGRE Consortium are listed in the Appendix on page 153.

Abstract

Objective

Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples.

Methods

We performed a combined analysis of the primary genome scan data of the Autism Genetic Resource Exchange (AGRE) and Finnish autism samples to reveal susceptibility loci potentially shared by these study samples.

Results

In the initial combined data analysis, the best loci (p < 0.05) were observed at 1p12-q25, 3p24-26, 4q21-31, 5p15-q12, 6q14-21, 7q33-36, 8q22-24, 17p12-q21, and 19p13-q13. The combined analysis of Finnish and AGRE families showed the most promising shared locus on 3p24-26 with nonparametric logarithm of odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide increased linkage evidence for the earlier identified loci on 3q25-27 or 17p12-q21. However, the 17p12-q21 locus remained promising also in the combined sample (NPLall =2.38, p = 0.0076).

Interpretation

Our study of 314 autism families highlights the importance of further analyses on 3p24-26 locus involving comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a positional and functional candidate gene for autism. Ann Neurol 2005

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