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A heterogeneity-based genome search meta-analysis for autism-spectrum disorders

Molecular Psychiatry volume 11, pages 29–36 (2006)Cite this article

Abstract

Autism and autism-spectrum disorders exhibit high heritability, although specific susceptibility genes still remain largely elusive. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) of nine genome scans on autism or autism-spectrum disorders. Each genome scan was separated in 30 cM bins and the maximum linkage statistic from each bin was ranked. Significance for each bin's average rank and for between-scan heterogeneity (dis-similarity in the average ranks) was obtained through Monte Carlo tests. For autism, data from 771 affected sibpairs were synthesized across six separate genome scans. Region 7q22–q32 reached genome-wide significance both in weighted and unweighted analyses, with evidence for significantly low between-scan heterogeneity. The flanking chromosomal region 7q32-qter reached the less stringent threshold of suggestive significance, with no evidence for low between-scan heterogeneity. For autism-spectrum disorders (634 affected sibpairs from five separate scans), no chromosomal region reached genome-wide significance. However, suggestive significance was reached for the chromosomal regions 17p11.2–q12 and 10p12–q11.1 in weighted analyses. There was evidence for significantly high between-scan heterogeneity for the former region. The meta-analysis suggests that the 7q22–q32 region should be further scrutinized for autism susceptibility genes, while autism-spectrum disorders seem to have quite diverse linkage signals across scans, possibly suggesting genetic heterogeneity across subsyndromes and subpopulations.

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Authors and Affiliations

  1. Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, University of Ioannina, Ioannina, Greece

    T A Trikalinos, A Karvouni & J P A Ioannidis

  2. Department of Medicine, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA, USA

    T A Trikalinos & J P A Ioannidis

  3. Biomathematics Unit, University of Thessaly School of Medicine, Larissa, Greece

    E Zintzaras

  4. Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

    T Ylisaukko-oja & L Peltonen

  5. Department of Medical Genetics, University of Helsinki, Helsinki, Finland

    T Ylisaukko-oja, L Peltonen & I Järvelä

  6. Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki, Finland

    I Järvelä

  7. Biomedical Research Institute, Foundation for Research and Technology Hellas–FORTH, Ioannina, Greece

    J P A Ioannidis

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  1. T A Trikalinos
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Trikalinos, T., Karvouni, A., Zintzaras, E. et al. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry 11, 29–36 (2006). https://doi.org/10.1038/sj.mp.4001750

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