Sex-specific association of a common variant of the XG gene with autism spectrum disorders

Authors

  • Shun-Chiao Chang,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts
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  • David L. Pauls,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    3. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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  • Christoph Lange,

    1. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
    2. Channing Laboratories, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    3. Institute for Genomic Mathematics, University of Bonn, Bonn, Germany
    4. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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  • Roksana Sasanfar,

    1. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    2. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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  • Susan L. Santangelo

    Corresponding author
    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    3. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    4. Department of Psychiatry, Maine Medical Center, Maine Medical Center Research Institute, Portland, Maine
    • Correspondence to:

      Susan L. Santangelo, Sc.D., Maine Medical Center and Maine Medical Center Research Institute, 932 Congress Street, Rm 224, Portland, ME 04102.

      E-mail: SSantangel@mmc.org

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  • The authors declare no biomedical financial interests or potential conflicts of interest.

Abstract

Autism spectrum disorders (ASD) are much more common in males than in females. Studies using both linkage and candidate gene association approaches have identified genetic variants specific to families in which all affected cases were male, suggesting that sex may interact with or otherwise influence the expression of specific genes in association with ASD. In this study, we specifically evaluated the sex-specific genetic effects of ASD with a family-based genome-wide association study approach using the data from the Autism Genetic Resource Exchange repository. We evaluated the male-specific genetic effects of ASD in 374 multiplex families of European ancestry in which all affected were male (male-only; MO) and identified a novel genome-wide significant association in the pseudoautosomal boundary on chromosome Xp22.33/Yp11.31 in the MO families of predominantly paternal origin (rs2535443, p = 3.8 × 10−8). Five markers that reside within a 550 kb intergenic region on chromosome 13q33.3, between the MYO16 and IRS2 genes, also showed suggestive association with ASD in the MO families (p = 3.3 × 10−5 to 5.3 × 10−7). In contrast, none of these markers appeared to be associated with ASD in the families containing any affected females. Our results suggest that the pseudoautosomal boundary on Xp22.33/Yp11.31 may harbor male-specific genetic variants for ASD. © 2013 Wiley Periodicals, Inc.

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