A Comparison of Univariate and Multivariate
Tests for Genetic Linkage.
Amos CI, Laing AE
Genetic Studies Section, NIAMS, Bethesda, MD 20892.
Genetic Epidemiology, 10(6):671-676(1993)
Abstract
A variety of robust and model-dependent genetic linkage methods were applied to log
transformed lipid levels from a large pedigree in which the LDL receptor defect has been
shown to segregate by molecular biologic techniques. Application of the
Haseman-Elston and a variance-components based test for linkage identified LDL and
cholesterol as cosegregating with the marker C3, which is genetically linked to the LDL
receptor defect. Consideration of lipid fractions as a multivariate response identified
(0.723 x cholesterol) - (0.551 x triglycerides) as most strongly supporting evidence for
linkage with C3. Subsequent segregation and linkage analyses provided support for an
autosomal dominant major gene influencing either LDL or the function of cholesterol
and triglycerides. Genetic linkage to LDL was only mildly supported, with a maximum
lod score of 0.51 at a recombination fraction of theta = 0.33. Genetic linkage of the linear
function to C3 was more strongly supported, with a maximum lod score of 1.69 at theta
= 0.09. Bivariate analysis of clinical affection (with either type IIa or type IIb
hyperlipidemia) and quantitative measures (LDL or the linear function) generally led to
decreased lod scores, indicating, in this pedigree, loss of information when using clinical
affection.
Variance component linkage analysis