Molecular Psychiatry
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2002, Volume 7, Number 1, Pages 56-66
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Original Research Article
Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7
J A Badner and E S Gershon

Department of Psychiatry, University of Chicago, Chicago, IL, USA

Correspondence to: J A Badner, MD, PhD, Department of Psychiatry, University of Chicago, 5841 South Maryland Ave, MC3077 Chicago, Illinois 60637, USA. E-mail: jbadner@yoda.bsd.uchicago.edu

Abstract

Although the concept of meta-analysis of multiple linkage scans of a genetic trait is not new, it can be difficult to apply to published data given the lack of consistency in the presentation of linkage results. In complex inheritance common diseases, there are many instances where one or two studies meet genome-wide criteria for significant or suggestive linkage but several other studies do not show even nominally significant results with the same region. One possibility for resolving differences between study results would be to combine an available result parameter of several studies. We describe here a method of regional meta-analysis, the multiple-scan probability (MSP), which can be used on published results. It combines the reported P-values of individual studies, after correcting each value for the size of the region containing a minimum P-value. Analyses of the power of MSP and of its type I error rates are presented. The type I error rate is at least as low as that for a single genome scan and thus genome-wide significance criteria may be applied. We also demonstrate appropriate criteria for this type of meta-analysis when the most significant study is included, and when that study is used to define a region of interest and then excluded. In our simulations, meta-analysis is at least as powerful as pooling data. Finally, we apply this method of meta-analysis to the evidence for linkage of autism susceptibility loci and demonstrate evidence for a susceptibility locus at 7q.

Molecular Psychiatry (2002) 7, 56-66. DOI: 10.1038/sj/mp/4000922

Keywords

meta-analysis; autism; genetic linkage analysis; complex genetic diseases; statistical data interpretation

Received 12 December 2000; revised 8 March 2001; accepted 12 March 2001
2002, Volume 7, Number 1, Pages 56-66
Table of contents    Previous  Abstract  Next   Full text  PDF