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 inherit ance 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 unreli able except as confirmation of either a significant linkage or a stron g candidate locus, A threshold as great as 4 is unnecessarily conserva tive if multipoint tests are used sensibly. Marker density is not a ma jor factor; and biases in the evaluation of LOD scores-especially inad equate allowance for estimation of nuisance parameters in multiple mod els-are paramount. Allelic association increases resolution for oligog enes within a candidate region and remains the only practical method t o Locate polygenes, The method sketched here combines multipoint linka ge and allelic association to test efficiently for a regional candidat e locus.