Marker genotyping errors in old data on X-linkage in bipolar illness

Abstract

Investigations of linkage markers of the X-chromosome colorblindness region in bipolar manic-depressive illness (BP) have yielded inconsistent results, with linkage accepted in some and rejected in other studies. Although genetic heterogeneity has been proposed as the reason for differences, other possibilities exist, including systematic procedural errors. Statistical evidence for linkage between the markers, Xg and colorblindness, is present in a series of papers on bipolar illness reported in 1972–1975. The linkage implied by this reanalysis is spurious, since the two markers are at opposite ends of the X chromosome. The presumptive reason for this spurious linkage is that it is a result of systematic genotyping errors. The support provided by these data to the X-linkage hypothesis in BP illness is thus diminished. That is, the linkage to illness may depend on systematic errors in marker genotyping. In general, the possible causes of inconsistency between linkage reports may be divided into statistical and systematic causes. Statistical causes would generally consist of chance differences in sampling, such as might occur under genetic heterogeneity. If this occurs, the reports rejecting linkage may be false negatives, or the reports detecting linkage may be false-positive results. Systematic causes of differences among reports could include systematic errors (or variations) in procedures, including ascertainment, diagnosis, genotyping, or analysis. Consistency of the marker map in a particular study with the known marker map is one test for systematic erros in genotyping.