Meta-analysis of linkage data under worst-case conditions: a demonstration using the human OB region

To date, few methods have been developed explicitly for meta-analysis of linkage analyses. Moreover, the methods that have been developed or suggested generally depend on certain ideal situations and have not been widely applied. In this article, we apply standard statistical theory and meta-analytic techniques in novel ways to five published papers discussing the evidence of linkage of body mass index (BMI) to the region of the human genome containing the OB gene. These methods are "inference based," meaning that they allow one to make statements about the statistical significance of the entire body of evidence. As currently developed, they do not allow specific statements to be made about the amount of variance explained by any putative locus or allow precise confidence intervals to be placed around the putative location of a linked locus. By applying these techniques to the literature on linkage in the human OB gene region, we are able to show that the evidence for linkage somewhere in the region is extremely strong (P = 1.5 x 10[-5]).