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Meta‐analysis in complex diseases

Meta-analysis implies combination of published or unpublished statistics from different studies on the same subject, in order to infer means and heterogeneity. For vahdity, the distribution of the statistics on the null hypothesis must be known, and there must be no bias towards samples supporting or contradicting the null hypothesis. Genetic mapping of monogenic diseases from multiple pairwise data is a prototype of metaanalysis, since each study provides an estimate of recombination and of the amount of information, whether expressed as equivalent number of meioses, a LOD score, or some other statistic. Sequential lods for linkage [1] were meta-analysis before the latter term was invented, as were the earlier metrics of Bernstein, Weiner, Haldane and Fisher. However, LODS (Z) are distinguished from other approaches by the theories of Wald [2] and Haldane and Smith [3] according to which