Significance levels in complex inheritance

A LOD score greater than or equal to 3 is necessary but not sufficient to make a linkage test reliable, anti this applies to complex inheritance as well as to major loci. Factors that affect this threshold are considered here, A LOD score as small as 2 is suggestive but is unreliable except as confirmation of either a significant linkage or a strong candidate locus, A threshold as great as 4 is unnecessarily conservative if multipoint tests are used sensibly. Marker density is not a major factor; and biases in the evaluation of LOD scores-especially inadequate allowance for estimation of nuisance parameters in multiple models-are paramount. Allelic association increases resolution for oligogenes within a candidate region and remains the only practical method to Locate polygenes, The method sketched here combines multipoint linkage and allelic association to test efficiently for a regional candidate locus.