title: Significance levels in complex inheritance.
abstract: A LOD score >=3 is necessary but not sufficient to make a linkage test reliable, and 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.
authors.affiliation: Human Genetics, University of Southampton, Anne Hospital, Southampton, United Kingdom. nem@soton.ac.uk
authors.forename: N E
authors.initials: NE
authors.lastname: Morton
mesh_terms: D000483:Alleles; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score
chemical_list: D005819:Genetic Markers