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Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD

Molecular Psychiatry volume 18, pages 137–138 (2013)Cite this article

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Current estimates of the heritability of autism spectrum disorders (ASD) derived from existing clinical twin studies1, 2, 3, 4 are potentially confounded by a number of factors, including low sample size, inconsistency in case definition and the role of de novo mutation (currently estimated to contribute to some 20% of cases), and the possibility that heritable causes of ASD in a twin could result in environmentally engendered affectation of a non-identical co-twin in utero, especially if mediated by humoral or immune mechanisms. To minimize these confounds, we compared autism recurrence in half siblings versus that in full siblings, using data (6 June 2011) from over five thousand families enrolled in the Interactive Autism Network (IAN), a national volunteer register for ASD, detailed characteristics of which have been previously described by our group.5, 6 Recurrence rate among full siblings was observed to be approximately twice that among half siblings, providing strong evidence of genetic transmission of ASD.

The data included 5237 families with (a) an ASD-affected child and (b) at least one additional sibling. Among these, 619 included at least one maternal half-sibling, 55 included a paternal half-sibling and 4832 contained at least one full sibling of an ASD proband. A maximum of one full sibling and one maternal half sibling per family (selected at random in families in which more were available) were incorporated into the analysis. Sample characteristics are provided in Supplementary Table 1.

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Authors and Affiliations

  1. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    J N Constantino, A Todorov, Y Zhang, E Molloy & R Fitzgerald

  2. Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA

    J N Constantino

  3. Program in Occupational Therapy, Washington University School of Medicine, St Louis, MO, USA

    C Hilton

  4. Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, USA

    P Law

  5. Department of Neurology, University of California, Los Angeles, CA, USA

    D Geschwind

  6. Department of Psychiatry and Human Genetics, University of California, Los Angeles, CA, USA

    D Geschwind

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  1. J N Constantino
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  2. A Todorov
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  3. C Hilton
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  4. P Law
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  5. Y Zhang
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  6. E Molloy
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  7. R Fitzgerald
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  8. D Geschwind
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Correspondence to J N Constantino.

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Constantino, J., Todorov, A., Hilton, C. et al. Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD. Mol Psychiatry 18, 137–138 (2013). https://doi.org/10.1038/mp.2012.9

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