Significance levels in complex inheritance

Am J Hum Genet. 1998 Mar;62(3):690-7. doi: 10.1086/301741.

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.

MeSH terms

  • Alleles
  • Genetic Linkage*
  • Genetic Markers
  • Humans
  • Lod Score*

Substances

  • Genetic Markers