1. ¹Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece
2. ²Department of Medicine, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA, USA
3. ³Biomathematics Unit, University of Thessaly School of Medicine, Larissa, Greece
4. ⁴Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
5. ⁵Department of Medical Genetics, University of Helsinki, Helsinki, Finland
6. ⁶Laboratory of Molecular Genetics, Helsinki University Central Hospital, Helsinki, Finland
7. ⁷Biomedical Research Institute, Foundation for Research and Technology Hellas–FORTH, Ioannina, Greece

Correspondence: Dr JPA Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. E-mail: jioannid@cc.uoi.gr

Received 6 July 2005; Revised 12 August 2005; Accepted 16 August 2005; Published online 27 September 2005.

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.