title: A heterogeneity-based genome search meta-analysis for autism-spectrum disorders.
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.
authors.affiliation: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.
authors.forename: T A
authors.initials: TA
authors.lastname: Trikalinos
authors.forename: A
authors.initials: A
authors.lastname: Karvouni
authors.forename: E
authors.initials: E
authors.lastname: Zintzaras
authors.forename: T
authors.initials: T
authors.lastname: Ylisaukko-oja
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
authors.forename: I
authors.initials: I
authors.lastname: Järvelä
authors.forename: J P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D020817:Asperger Syndrome / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D018740:Genetic Heterogeneity; D015894:Genome, Human; D023281:Genomics; D006801:Humans