Mapping oligogenes for atopy and asthma by meta-analysis

meta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. reporting is biassed, and nonsignificance is seldom quantified. therefore meta-analysis cannot identify oligogenes within a candidate region nor establish their significance, but it defines candidate regions well. applied to a database on atopy and asthma, candidate regions are identified on chromosomes 6, 5, 16, 11, 12, 13, 14, 7, 20, and 10, in rank order from strongest to weakest evidence. on the other hand, there is little support for chromosomes 9, 8, 18, 1, and 15 in the same rank order. the evidence from 156 publications is reviewed for each region. with reasonable type i and ii errors several thousand affected sib pairs would be required to detect a locus accounting for 1/10 of the genetic effect on asthma. identification of regions by a genome scan for linkage and allelic association requires international collaborative studies to reach the necessary sample size, using lod-based methods that specify a weakly parametric alternative hypothesis and can be combined over studies that differ in ascertainment, phenotypes, and markers. this has become the central problem in complex inheritance.